Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome
Identifieur interne : 002586 ( Pmc/Curation ); précédent : 002585; suivant : 002587Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome
Auteurs : Fadi J. Charchar [Australie] ; Lisa Ds Bloomer [Royaume-Uni] ; Timothy A. Barnes [Royaume-Uni] ; Mark J. Cowley [Australie] ; Christopher P. Nelson [Royaume-Uni] ; Yanzhong Wang [Royaume-Uni] ; Matthew Denniff [Royaume-Uni] ; Radoslaw Debiec [Royaume-Uni] ; Paraskevi Christofidou [Royaume-Uni] ; Scott Nankervis [Australie] ; Anna F. Dominiczak [Royaume-Uni] ; Ahmed Bani-Mustafa [Australie] ; Anthony J. Balmforth [Royaume-Uni] ; Alistair S. Hall [Royaume-Uni] ; Jeanette Erdmann [Allemagne] ; Francois Cambien [France] ; Panos Deloukas [Royaume-Uni] ; Christian Hengstenberg [Allemagne] ; Chris Packard [Royaume-Uni] ; Heribert Schunkert [Allemagne] ; Willem H. Ouwehand [Royaume-Uni] ; Ian Ford [Royaume-Uni] ; Alison H. Goodall [Royaume-Uni] ; Mark A. Jobling [Royaume-Uni] ; Nilesh J. Samani [Royaume-Uni] ; Maciej Tomaszewski [Royaume-Uni]Source :
- Lancet [ 0140-6736 ] ; 2012.
Abstract
A sexual dimorphism exists in the incidence and prevalence of coronary artery disease—men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity.
We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study.
Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95% CI 1·20–2·54, p=0·004), WOSCOPS (1·45, 1·08–1·95, p=0·012), and joint analysis of both populations (1·56, 1·24–1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis.
The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation.
British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust.
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DOI: 10.1016/S0140-6736(11)61453-0
PubMed: 22325189
PubMed Central: 3314981
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Dominiczak</name><affiliation wicri:level="1"><nlm:aff id="aff6">Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea></affiliation></author><author><name sortKey="Bani Mustafa, Ahmed" sort="Bani Mustafa, Ahmed" uniqKey="Bani Mustafa A" first="Ahmed" last="Bani-Mustafa">Ahmed Bani-Mustafa</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Health Sciences, University of Ballarat, Ballarat, VIC, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Health Sciences, University of Ballarat, Ballarat, VIC</wicri:regionArea></affiliation></author><author><name sortKey="Balmforth, Anthony J" sort="Balmforth, Anthony J" uniqKey="Balmforth A" first="Anthony J" last="Balmforth">Anthony J. Balmforth</name><affiliation wicri:level="1"><nlm:aff id="aff9">Division of Epidemiology, LIGHT, School of Medicine, University of Leeds, Leeds, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Epidemiology, LIGHT, School of Medicine, University of Leeds, Leeds</wicri:regionArea></affiliation></author><author><name sortKey="Hall, Alistair S" sort="Hall, Alistair S" uniqKey="Hall A" first="Alistair S" last="Hall">Alistair S. 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Ouwehand</name><affiliation wicri:level="1"><nlm:aff id="aff12">Wellcome Trust Sanger Institute, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff14">Department of Haematology, University of Cambridge and National Health Service Blood and Transplant, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge and National Health Service Blood and Transplant, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name><affiliation wicri:level="1"><nlm:aff id="aff7">Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Robertson Centre for Biostatistics, University of Glasgow, Glasgow</wicri:regionArea></affiliation></author><author><name sortKey="Goodall, Alison H" sort="Goodall, Alison H" uniqKey="Goodall A" first="Alison H" last="Goodall">Alison H. Goodall</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff15">National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Jobling, Mark A" sort="Jobling, Mark A" uniqKey="Jobling M" first="Mark A" last="Jobling">Mark A. Jobling</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Genetics, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Genetics, University of Leicester, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J" last="Samani">Nilesh J. Samani</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff15">National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Tomaszewski, Maciej" sort="Tomaszewski, Maciej" uniqKey="Tomaszewski M" first="Maciej" last="Tomaszewski">Maciej Tomaszewski</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff15">National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22325189</idno><idno type="pmc">3314981</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314981</idno><idno type="RBID">PMC:3314981</idno><idno type="doi">10.1016/S0140-6736(11)61453-0</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">002736</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002736</idno><idno type="wicri:Area/Pmc/Curation">002586</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002586</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome</title><author><name sortKey="Charchar, Fadi J" sort="Charchar, Fadi J" uniqKey="Charchar F" first="Fadi J" last="Charchar">Fadi J. Charchar</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Health Sciences, University of Ballarat, Ballarat, VIC, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Health Sciences, University of Ballarat, Ballarat, VIC</wicri:regionArea></affiliation></author><author><name sortKey="Bloomer, Lisa Ds" sort="Bloomer, Lisa Ds" uniqKey="Bloomer L" first="Lisa Ds" last="Bloomer">Lisa Ds Bloomer</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Barnes, Timothy A" sort="Barnes, Timothy A" uniqKey="Barnes T" first="Timothy A" last="Barnes">Timothy A. Barnes</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Cowley, Mark J" sort="Cowley, Mark J" uniqKey="Cowley M" first="Mark J" last="Cowley">Mark J. Cowley</name><affiliation wicri:level="1"><nlm:aff id="aff4">Peter Wills Bioinformatics Centre, Garvan Institute for Medical Research, Sydney, NSW, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Peter Wills Bioinformatics Centre, Garvan Institute for Medical Research, Sydney, NSW</wicri:regionArea></affiliation></author><author><name sortKey="Nelson, Christopher P" sort="Nelson, Christopher P" uniqKey="Nelson C" first="Christopher P" last="Nelson">Christopher P. Nelson</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff15">National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yanzhong" sort="Wang, Yanzhong" uniqKey="Wang Y" first="Yanzhong" last="Wang">Yanzhong Wang</name><affiliation wicri:level="1"><nlm:aff id="aff5">Division of Health and Social Care Research, King's College London, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Health and Social Care Research, King's College London, London</wicri:regionArea></affiliation></author><author><name sortKey="Denniff, Matthew" sort="Denniff, Matthew" uniqKey="Denniff M" first="Matthew" last="Denniff">Matthew Denniff</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Debiec, Radoslaw" sort="Debiec, Radoslaw" uniqKey="Debiec R" first="Radoslaw" last="Debiec">Radoslaw Debiec</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Christofidou, Paraskevi" sort="Christofidou, Paraskevi" uniqKey="Christofidou P" first="Paraskevi" last="Christofidou">Paraskevi Christofidou</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Nankervis, Scott" sort="Nankervis, Scott" uniqKey="Nankervis S" first="Scott" last="Nankervis">Scott Nankervis</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Health Sciences, University of Ballarat, Ballarat, VIC, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Health Sciences, University of Ballarat, Ballarat, VIC</wicri:regionArea></affiliation></author><author><name sortKey="Dominiczak, Anna F" sort="Dominiczak, Anna F" uniqKey="Dominiczak A" first="Anna F" last="Dominiczak">Anna F. Dominiczak</name><affiliation wicri:level="1"><nlm:aff id="aff6">Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow</wicri:regionArea></affiliation></author><author><name sortKey="Bani Mustafa, Ahmed" sort="Bani Mustafa, Ahmed" uniqKey="Bani Mustafa A" first="Ahmed" last="Bani-Mustafa">Ahmed Bani-Mustafa</name><affiliation wicri:level="1"><nlm:aff id="aff1">School of Health Sciences, University of Ballarat, Ballarat, VIC, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Health Sciences, University of Ballarat, Ballarat, VIC</wicri:regionArea></affiliation></author><author><name sortKey="Balmforth, Anthony J" sort="Balmforth, Anthony J" uniqKey="Balmforth A" first="Anthony J" last="Balmforth">Anthony J. Balmforth</name><affiliation wicri:level="1"><nlm:aff id="aff9">Division of Epidemiology, LIGHT, School of Medicine, University of Leeds, Leeds, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Epidemiology, LIGHT, School of Medicine, University of Leeds, Leeds</wicri:regionArea></affiliation></author><author><name sortKey="Hall, Alistair S" sort="Hall, Alistair S" uniqKey="Hall A" first="Alistair S" last="Hall">Alistair S. Hall</name><affiliation wicri:level="1"><nlm:aff id="aff9">Division of Epidemiology, LIGHT, School of Medicine, University of Leeds, Leeds, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Division of Epidemiology, LIGHT, School of Medicine, University of Leeds, Leeds</wicri:regionArea></affiliation></author><author><name sortKey="Erdmann, Jeanette" sort="Erdmann, Jeanette" uniqKey="Erdmann J" first="Jeanette" last="Erdmann">Jeanette Erdmann</name><affiliation wicri:level="1"><nlm:aff id="aff10">Universität zu Lübeck, Medizinische Klinik II, Lübeck, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Universität zu Lübeck, Medizinische Klinik II, Lübeck</wicri:regionArea></affiliation></author><author><name sortKey="Cambien, Francois" sort="Cambien, Francois" uniqKey="Cambien F" first="Francois" last="Cambien">Francois Cambien</name><affiliation wicri:level="1"><nlm:aff id="aff11">INSERM UMRS 937, Pierre and Marie Curie University and Medical School, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM UMRS 937, Pierre and Marie Curie University and Medical School, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Deloukas, Panos" sort="Deloukas, Panos" uniqKey="Deloukas P" first="Panos" last="Deloukas">Panos Deloukas</name><affiliation wicri:level="1"><nlm:aff id="aff12">Wellcome Trust Sanger Institute, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Hengstenberg, Christian" sort="Hengstenberg, Christian" uniqKey="Hengstenberg C" first="Christian" last="Hengstenberg">Christian Hengstenberg</name><affiliation wicri:level="1"><nlm:aff id="aff13">Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg</wicri:regionArea></affiliation></author><author><name sortKey="Packard, Chris" sort="Packard, Chris" uniqKey="Packard C" first="Chris" last="Packard">Chris Packard</name><affiliation wicri:level="1"><nlm:aff id="aff8">College of Medicine, Veterinary and Life Sciences, and Department of Vascular Biochemistry, University of Glasgow, Glasgow, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>College of Medicine, Veterinary and Life Sciences, and Department of Vascular Biochemistry, University of Glasgow, Glasgow</wicri:regionArea></affiliation></author><author><name sortKey="Schunkert, Heribert" sort="Schunkert, Heribert" uniqKey="Schunkert H" first="Heribert" last="Schunkert">Heribert Schunkert</name><affiliation wicri:level="1"><nlm:aff id="aff10">Universität zu Lübeck, Medizinische Klinik II, Lübeck, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Universität zu Lübeck, Medizinische Klinik II, Lübeck</wicri:regionArea></affiliation></author><author><name sortKey="Ouwehand, Willem H" sort="Ouwehand, Willem H" uniqKey="Ouwehand W" first="Willem H" last="Ouwehand">Willem H. Ouwehand</name><affiliation wicri:level="1"><nlm:aff id="aff12">Wellcome Trust Sanger Institute, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Cambridge</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff14">Department of Haematology, University of Cambridge and National Health Service Blood and Transplant, Cambridge, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Haematology, University of Cambridge and National Health Service Blood and Transplant, Cambridge</wicri:regionArea></affiliation></author><author><name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name><affiliation wicri:level="1"><nlm:aff id="aff7">Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Robertson Centre for Biostatistics, University of Glasgow, Glasgow</wicri:regionArea></affiliation></author><author><name sortKey="Goodall, Alison H" sort="Goodall, Alison H" uniqKey="Goodall A" first="Alison H" last="Goodall">Alison H. Goodall</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff15">National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Jobling, Mark A" sort="Jobling, Mark A" uniqKey="Jobling M" first="Mark A" last="Jobling">Mark A. Jobling</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Genetics, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Genetics, University of Leicester, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Samani, Nilesh J" sort="Samani, Nilesh J" uniqKey="Samani N" first="Nilesh J" last="Samani">Nilesh J. Samani</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff15">National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester</wicri:regionArea></affiliation></author><author><name sortKey="Tomaszewski, Maciej" sort="Tomaszewski, Maciej" uniqKey="Tomaszewski M" first="Maciej" last="Tomaszewski">Maciej Tomaszewski</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Cardiovascular Sciences, University of Leicester, Leicester</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff15">National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester</wicri:regionArea></affiliation></author></analytic><series><title level="j">Lancet</title><idno type="ISSN">0140-6736</idno><idno type="eISSN">1474-547X</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><sec><title>Background</title><p>A sexual dimorphism exists in the incidence and prevalence of coronary artery disease—men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity.</p></sec><sec><title>Methods</title><p>We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study.</p></sec><sec><title>Findings</title><p>Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95% CI 1·20–2·54, p=0·004), WOSCOPS (1·45, 1·08–1·95, p=0·012), and joint analysis of both populations (1·56, 1·24–1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis.</p></sec><sec><title>Interpretation</title><p>The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation.</p></sec><sec><title>Funding</title><p>British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Skaletsky, H" uniqKey="Skaletsky H">H Skaletsky</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Lancet</journal-id><journal-id journal-id-type="iso-abbrev">Lancet</journal-id><journal-title-group><journal-title>Lancet</journal-title></journal-title-group><issn pub-type="ppub">0140-6736</issn><issn pub-type="epub">1474-547X</issn><publisher><publisher-name>Lancet Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22325189</article-id><article-id pub-id-type="pmc">3314981</article-id><article-id pub-id-type="publisher-id">LANCET61453</article-id><article-id pub-id-type="doi">10.1016/S0140-6736(11)61453-0</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Charchar</surname><given-names>Fadi J</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Bloomer</surname><given-names>Lisa DS</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Barnes</surname><given-names>Timothy A</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Cowley</surname><given-names>Mark J</given-names></name><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author"><name><surname>Nelson</surname><given-names>Christopher P</given-names></name><xref rid="aff2" ref-type="aff">b</xref><xref rid="aff15" ref-type="aff">o</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Yanzhong</given-names></name><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author"><name><surname>Denniff</surname><given-names>Matthew</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Debiec</surname><given-names>Radoslaw</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Christofidou</surname><given-names>Paraskevi</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Nankervis</surname><given-names>Scott</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Dominiczak</surname><given-names>Anna F</given-names></name><xref rid="aff6" ref-type="aff">f</xref></contrib><contrib contrib-type="author"><name><surname>Bani-Mustafa</surname><given-names>Ahmed</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Balmforth</surname><given-names>Anthony J</given-names></name><xref rid="aff9" ref-type="aff">i</xref></contrib><contrib contrib-type="author"><name><surname>Hall</surname><given-names>Alistair S</given-names></name><xref rid="aff9" ref-type="aff">i</xref></contrib><contrib contrib-type="author"><name><surname>Erdmann</surname><given-names>Jeanette</given-names></name><xref rid="aff10" ref-type="aff">j</xref></contrib><contrib contrib-type="author"><name><surname>Cambien</surname><given-names>Francois</given-names></name><xref rid="aff11" ref-type="aff">k</xref></contrib><contrib contrib-type="author"><name><surname>Deloukas</surname><given-names>Panos</given-names></name><xref rid="aff12" ref-type="aff">l</xref></contrib><contrib contrib-type="author"><name><surname>Hengstenberg</surname><given-names>Christian</given-names></name><xref rid="aff13" ref-type="aff">m</xref></contrib><contrib contrib-type="author"><name><surname>Packard</surname><given-names>Chris</given-names></name><xref rid="aff8" ref-type="aff">h</xref></contrib><contrib contrib-type="author"><name><surname>Schunkert</surname><given-names>Heribert</given-names></name><xref rid="aff10" ref-type="aff">j</xref></contrib><contrib contrib-type="author"><name><surname>Ouwehand</surname><given-names>Willem H</given-names></name><xref rid="aff12" ref-type="aff">l</xref><xref rid="aff14" ref-type="aff">n</xref></contrib><contrib contrib-type="author"><name><surname>Ford</surname><given-names>Ian</given-names></name><xref rid="aff7" ref-type="aff">g</xref></contrib><contrib contrib-type="author"><name><surname>Goodall</surname><given-names>Alison H</given-names></name><xref rid="aff2" ref-type="aff">b</xref><xref rid="aff15" ref-type="aff">o</xref></contrib><contrib contrib-type="author"><name><surname>Jobling</surname><given-names>Mark A</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author"><name><surname>Samani</surname><given-names>Nilesh J</given-names></name><xref rid="aff2" ref-type="aff">b</xref><xref rid="aff15" ref-type="aff">o</xref></contrib><contrib contrib-type="author"><name><surname>Tomaszewski</surname><given-names>Maciej</given-names></name><email>mt142@le.ac.uk</email><xref rid="aff2" ref-type="aff">b</xref><xref rid="aff15" ref-type="aff">o</xref><xref rid="cor1" ref-type="corresp">*</xref></contrib></contrib-group><aff id="aff1"><label>a</label>School of Health Sciences, University of Ballarat, Ballarat, VIC, Australia</aff><aff id="aff2"><label>b</label>Department of Cardiovascular Sciences, University of Leicester, Leicester, UK</aff><aff id="aff3"><label>c</label>Department of Genetics, University of Leicester, Leicester, UK</aff><aff id="aff4"><label>d</label>Peter Wills Bioinformatics Centre, Garvan Institute for Medical Research, Sydney, NSW, Australia</aff><aff id="aff5"><label>e</label>Division of Health and Social Care Research, King's College London, London, UK</aff><aff id="aff6"><label>f</label>Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK</aff><aff id="aff7"><label>g</label>Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK</aff><aff id="aff8"><label>h</label>College of Medicine, Veterinary and Life Sciences, and Department of Vascular Biochemistry, University of Glasgow, Glasgow, UK</aff><aff id="aff9"><label>i</label>Division of Epidemiology, LIGHT, School of Medicine, University of Leeds, Leeds, UK</aff><aff id="aff10"><label>j</label>Universität zu Lübeck, Medizinische Klinik II, Lübeck, Germany</aff><aff id="aff11"><label>k</label>INSERM UMRS 937, Pierre and Marie Curie University and Medical School, Paris, France</aff><aff id="aff12"><label>l</label>Wellcome Trust Sanger Institute, Cambridge, UK</aff><aff id="aff13"><label>m</label>Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany</aff><aff id="aff14"><label>n</label>Department of Haematology, University of Cambridge and National Health Service Blood and Transplant, Cambridge, UK</aff><aff id="aff15"><label>o</label>National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, UK</aff><author-notes><corresp id="cor1"><label>*</label>Correspondence to: Dr Maciej Tomaszewski, Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK <email>mt142@le.ac.uk</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>10</day><month>3</month><year>2012</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
<pub-date pub-type="ppub"><day>10</day><month>3</month><year>2012</year></pub-date><volume>379</volume><issue>9819</issue><fpage>915</fpage><lpage>922</lpage><permissions><copyright-statement>© 2012 Elsevier Ltd. All rights reserved.</copyright-statement><copyright-year>2012</copyright-year><copyright-holder>Elsevier Ltd</copyright-holder><license><license-p>This document may be redistributed and reused, subject to <ext-link ext-link-type="uri" xlink:href="http://www.elsevier.com/wps/find/authorsview.authors/supplementalterms1.0">certain conditions</ext-link>.</license-p></license></permissions><abstract><title>Summary</title><sec><title>Background</title><p>A sexual dimorphism exists in the incidence and prevalence of coronary artery disease—men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity.</p></sec><sec><title>Methods</title><p>We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study.</p></sec><sec><title>Findings</title><p>Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95% CI 1·20–2·54, p=0·004), WOSCOPS (1·45, 1·08–1·95, p=0·012), and joint analysis of both populations (1·56, 1·24–1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis.</p></sec><sec><title>Interpretation</title><p>The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation.</p></sec><sec><title>Funding</title><p>British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust.</p></sec></abstract></article-meta></front><floats-group><fig id="fig1"><label>Figure 1</label><caption><p>Phylogenetic tree of the Y chromosome and frequency of haplogroups in the British Heart Foundation Family Heart Study (BHF-FHS) and West of Scotland Coronary Prevention Study (WOSCOPS)</p><p>Each vertical line represents one branch (haplogroup) of the Y chromosome phylogenetic tree. The 13 most common Y chromosome haplogroups are shown and are lined up from the phylogentically oldest on the left (Y[xBR]) to the youngest on the right (R1b1b2). The vertical length or height of each line corresponds to the age of each haplogroup (the longest line being the oldest haplogroup). The symbols at the top of each line (SRY10831.1, M35, M89, M201, M170, M304, M9, M45, M207, M173, SRY10831.2, and M269) are the identification numbers of the single nucleotide polymorphisms that define specific haplogroups according to the Y Chromosome Consortium nomenclature. The numbers in boxes reflect prevalence (percentage) of each haplogroup in BHF-FHS (upper row) and WOSCOPS (lower row) populations.</p></caption><graphic xlink:href="gr1"></graphic></fig><fig id="fig2"><label>Figure 2</label><caption><p>Immune pathways showing significant (false discovery rate <20%) differential expression in macrophages from men with haplogroup I compared with carriers of all other haplogroups</p><p>Red nodes show upregulated pathways and blue nodes show downregulated pathways in men with haplogroup I from the Kyoto Encyclopedia of Genes and Genomes. Node size is a function of the number of genes in each pathway (the larger the node, the more genes in the pathway) and the colour intensity of each node reflects the level of significance. Lines represent a network of biological links between the pathways; the thickness of each line is proportional to number of genes shared by pathways connected by the line. The high interconnection between these pathways suggests that they are not independent and represent different, yet overlapping, facets of immunity (<xref rid="sec1" ref-type="sec">webappendix pp 9–13</xref>). The image was generated with the Enrichment Map plugin for Cytoscape. ECM=extracellular matrix.</p></caption><graphic xlink:href="gr2"></graphic></fig><table-wrap id="tbl1" position="float"><label>Table 1</label><caption><p>Characteristics of men from British Heart Foundation Family Heart Study (BHF-FHS) and West of Scotland Coronary Prevention Study (WOSCOPS) stratified by case-control status</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th align="left"><bold>Cases</bold></th><th align="left"><bold>Controls</bold></th><th align="left"><bold>p value</bold></th></tr></thead><tbody><tr><td colspan="4" align="left"><bold>BHF-FHS</bold></td></tr><tr><td align="left">n</td><td align="left">811</td><td align="left">633</td><td align="left">..</td></tr><tr><td align="left">Age (years)</td><td align="left">60·6 (7·5)</td><td align="left">45·5 (11·7)</td><td align="left"><0·0001</td></tr><tr><td colspan="4" align="left"><bold>WOSCOPS</bold></td></tr><tr><td align="left">n</td><td align="left">482</td><td align="left">1052</td><td align="left">..</td></tr><tr><td align="left">Age (years)</td><td align="left">56·9 (5·1)</td><td align="left">56·8 (5·2)</td><td align="left">0·533</td></tr><tr><td align="left">Body-mass index (kg/m<sup>2</sup>)</td><td align="left">26·0 (3·2)</td><td align="left">25·6 (3·2)</td><td align="left">0·026</td></tr><tr><td align="left">Systolic blood pressure (mm Hg)</td><td align="left">139·5 (17·2)</td><td align="left">135·7 (17·1)</td><td align="left">0·0001</td></tr><tr><td align="left">Diastolic blood pressure (mm Hg)</td><td align="left">85·5 (10·5)</td><td align="left">83·7 (10·2)</td><td align="left">0·001</td></tr><tr><td align="left">HDL cholesterol (mmol/L)</td><td align="left">1·1 (0·2)</td><td align="left">1·1 (0·3)</td><td align="left"><0·0001</td></tr><tr><td align="left">LDL cholesterol (mmol/L)</td><td align="left">5·0 (0·5)</td><td align="left">4·9 (0·4)</td><td align="left">0·004</td></tr><tr><td align="left">Triglycerides (mmol/L)</td><td align="left">2·1 (1·6 to 2·8)</td><td align="left">1·9 (1·5 to 2·6)</td><td align="left">0·005</td></tr><tr><td align="left">Pravastatin-based treatment</td><td align="left">194 (40%)</td><td align="left">539 (51%)</td><td align="left">0·0001</td></tr><tr><td align="left">Glucose (mmol/L)</td><td align="left">4·9 (0·7)</td><td align="left">4·8 (0·7)</td><td align="left">0·025</td></tr><tr><td align="left">Diabetes</td><td align="left">9 (2%)</td><td align="left">13 (1%)</td><td align="left">0·464</td></tr><tr><td align="left">C-reactive protein (mg/L)</td><td align="left">2·7 (1·2 to 4·9)</td><td align="left">1·9 (0·9 to 3·9)</td><td align="left"><0·0001</td></tr><tr><td align="left">Smoking</td><td align="left">258 (54%)</td><td align="left">581 (55%)</td><td align="left">0·571</td></tr><tr><td align="left">Alcohol consumption ≥20 units per week</td><td align="left">79 (16%)</td><td align="left">186 (18%)</td><td align="left">0·584</td></tr><tr><td align="left">Carstairs deprivation index<xref rid="tbl1fn1" ref-type="table-fn">*</xref></td><td align="left">0·4 (−1·7 to 3·0)</td><td align="left">0·5 (−1·8 to 3·0)</td><td align="left">0·943</td></tr><tr><td align="left">Highest educational attainment<xref rid="tbl1fn2" ref-type="table-fn">†</xref></td><td align="left">1·6 (0·9)</td><td align="left">1·7 (0·9)</td><td align="left">0·784</td></tr><tr><td align="left">In employment</td><td align="left">304 (63%)</td><td align="left">690 (66%)</td><td align="left">0·338</td></tr></tbody></table><table-wrap-foot><fn><p>Data are n (%), mean (SD), or median (IQR).</p></fn></table-wrap-foot><table-wrap-foot><fn id="tbl1fn1"><label>*</label><p>Continuously scored measure based on four factors: lack of car ownership; Registrar General's Social Class classification of IV or V; overcrowded households; and male unemployment.</p></fn></table-wrap-foot><table-wrap-foot><fn id="tbl1fn2"><label>†</label><p>Average score based on four categories: secondary school with leaving certificate (no graduation); school leaving certificate (with graduation); further education, but no degree; and university degree or similar.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tbl2" position="float"><label>Table 2</label><caption><p>Characteristics of men from British Heart Foundation Family Heart Study (BHF-FHS) and West of Scotland Coronary Prevention Study (WOSCOPS) stratified by Y chromosome haplogroup status</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th align="left"><bold>Haplogroup I</bold></th><th align="left"><bold>Other haplogroups</bold></th><th align="left"><bold>p value</bold></th></tr></thead><tbody><tr><td colspan="4" align="left"><bold>BHF-FHS</bold></td></tr><tr><td align="left">n</td><td align="left">246</td><td align="left">1198</td><td align="left">..</td></tr><tr><td align="left">Age (years)</td><td align="left">55·8 (11·2)</td><td align="left">53·6 (12·3)</td><td align="left">0·006</td></tr><tr><td colspan="4" align="left"><bold>WOSCOPS</bold></td></tr><tr><td align="left">n</td><td align="left">228</td><td align="left">1306</td><td align="left">..</td></tr><tr><td align="left">Age (years)</td><td align="left">57·3 (5·2)</td><td align="left">56·7 (5·2)</td><td align="left">0·133</td></tr><tr><td align="left">Body-mass index (kg/m<sup>2</sup>)</td><td align="left">25·6 (3·7)</td><td align="left">25·8 (3·1)</td><td align="left">0·469</td></tr><tr><td align="left">Systolic blood pressure (mm Hg)</td><td align="left">138·0 (15·9)</td><td align="left">136·7 (17·4)</td><td align="left">0·284</td></tr><tr><td align="left">Diastolic blood pressure (mm Hg)</td><td align="left">84·2 (10·1)</td><td align="left">84·2 (10·4)</td><td align="left">0·987</td></tr><tr><td align="left">HDL cholesterol (mmol/L)</td><td align="left">1·1 (0·3)</td><td align="left">1·1 (0·3)</td><td align="left">0·310</td></tr><tr><td align="left">LDL cholesterol (mmol/L)</td><td align="left">5·0 (0·5)</td><td align="left">5·0 (0·4)</td><td align="left">0·514</td></tr><tr><td align="left">Triglycerides (mmol/L)</td><td align="left">1·9 (1·6 to 2·6)</td><td align="left">1·9 (1·5 to 2·6)</td><td align="left">0·481</td></tr><tr><td align="left">Pravastatin-based treatment</td><td align="left">110 (48%)</td><td align="left">623 (48%)</td><td align="left">0·937</td></tr><tr><td align="left">Glucose (mmol/L)</td><td align="left">4·9 (0·8)</td><td align="left">4·8 (0·7)</td><td align="left">0·243</td></tr><tr><td align="left">Diabetes</td><td align="left">6 (3%)</td><td align="left">16 (1%)</td><td align="left">0·179</td></tr><tr><td align="left">C-reactive protein (mg/L)</td><td align="left">2·1 (1·1 to 4·0)</td><td align="left">2·1 (1·0 to 4·3)</td><td align="left">0·659</td></tr><tr><td align="left">Smoking</td><td align="left">115 (50%)</td><td align="left">724 (55%)</td><td align="left">0·185</td></tr><tr><td align="left">Alcohol consumption ≥20 units per week</td><td align="left">34 (15%)</td><td align="left">231 (18%)</td><td align="left">0·353</td></tr><tr><td align="left">Carstairs deprivation index<xref rid="tbl2fn1" ref-type="table-fn">*</xref></td><td align="left">0·1 (−1·9 to 2·8)</td><td align="left">0·5 (−1·7 to 3·0)</td><td align="left">0·087</td></tr><tr><td align="left">Highest educational attainment<xref rid="tbl2fn2" ref-type="table-fn">†</xref></td><td align="left">1·7 (0·9)</td><td align="left">1·6 (0·9)</td><td align="left">0·189</td></tr><tr><td align="left">In employment</td><td align="left">156 (68%)</td><td align="left">838 (64%)</td><td align="left">0·214</td></tr></tbody></table><table-wrap-foot><fn><p>Data are n (%), mean (SD), or median (IQR).</p></fn></table-wrap-foot><table-wrap-foot><fn id="tbl2fn1"><label>*</label><p>Continuously scored measure based on four factors: lack of car ownership; Registrar General's Social Class classification of IV or V; overcrowded households; and male unemployment.</p></fn></table-wrap-foot><table-wrap-foot><fn id="tbl2fn2"><label>†</label><p>Average score based on four categories: secondary school with leaving certificate (no graduation); school leaving certificate (with graduation); further education, but no degree; and university degree or similar.</p></fn></table-wrap-foot></table-wrap><boxed-text id="box1"><label>Panel</label><caption><title>Research in context</title></caption><p><bold>Systematic review</bold></p><p>We searched original English-language publications in PubMed to May, 2011, using “Y chromosome”, “haplogroup”, “haplotype”, and “coronary artery disease” as keywords and found no studies that investigated the association between paternal lineages of the Y chromosome (haplogroups) and predisposition to coronary artery disease.</p><p><bold>Interpretation</bold></p><p>Our study is the first robust analysis of association between different lineages of the Y chromosome and coronary artery disease. We show that men who inherit haplogroup I (one of the most common Y chromosome types in Europe) from their male ancestors have a roughly 50% higher risk of coronary artery disease than do men with other types of the Y chromosome. The effect of haplogroup I on coronary artery disease is not mediated by traditional cardiovascular risk factors such as age, body-mass index, blood pressure, lipids, diabetes, smoking, alcohol consumption, socioeconomic status, or circulating concentrations of C-reactive protein. However, we noted that men with haplogroup I showed downregulation of adaptive immunity as well as upregulation of inflammatory response pathways in their macrophages compared with carriers of other Y chromosome types. These data show that predisposition to coronary artery disease in men might, at least in part, be determined by the paternal lineage of their Y chromosome and that this effect on risk of coronary artery disease is most likely mediated through immune response.</p></boxed-text></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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