Epidemiology and Genetic Epidemiology of the Liver Function Test Proteins
Identifieur interne : 006304 ( Main/Exploration ); précédent : 006303; suivant : 006305Epidemiology and Genetic Epidemiology of the Liver Function Test Proteins
Auteurs : Nilufer Rahmioglu [Royaume-Uni] ; Toby Andrew [Royaume-Uni] ; Lynn Cherkas [Royaume-Uni] ; Gabriela Surdulescu [Royaume-Uni] ; Ramasamyiyer Swaminathan [Royaume-Uni] ; Tim Spector [Royaume-Uni] ; Kourosh R. Ahmadi [Royaume-Uni]Source :
- PLoS ONE [ 1932-6203 ] ; 2009.
Abstract
The liver function test (LFT) is among the most commonly used clinical investigations to assess hepatic function, severity of liver diseases and the effect of therapies, as well as to detect drug-induced liver injury (DILI).
To determine the relative contribution of genetic and environmental factors as well as test and quantify the effects of sex, age, BMI and alcohol consumption to variation in liver function test proteins - including alanine amino transaminase (ALT), Albumin, gamma glutamyl transpeptidase (GGT), total bilirubin, total protein, total globulin, aspartate transaminase (AST), and alkaline phosphotase (ALP) - using the classical twin model.
Blood samples were collected from a total of 5380 twin pairs from the TwinsUK registry. We measured the expression levels of major proteins associated with the LFT, calculated BMI from measured weight and height and questionnaires were completed for alcohol consumption by the twins. The relative contribution of genetic and environmental factors to variation in the LFT proteins was assessed and quantified using a variance components model fitting approach.
Our results show that (1) variation in all the LFTs has a significant heritable basis (h2 ranging from 20% to 77%); (2) other than GGT, the LFTs are all affected to some extent by common environmental factors (c2 ranging from 24% to 54%); and (3) a small but significant proportion of the variation in the LFTs was due to confounding effects of age, sex, BMI, and alcohol use.
Variation in the LFT proteins is under significant genetic and common environmental control although sex, alcohol use, age and BMI also contribute significantly to inter-individual variation in the LFT proteins. Understanding the underlying genetic contribution of liver function tests may help the interpretation of their results and explain wide variation among individuals.
Url:
DOI: 10.1371/journal.pone.0004435
PubMed: 19209234
PubMed Central: 2636884
Affiliations:
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type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Cherkas, Lynn" sort="Cherkas, Lynn" uniqKey="Cherkas L" first="Lynn" last="Cherkas">Lynn Cherkas</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Surdulescu, Gabriela" sort="Surdulescu, Gabriela" uniqKey="Surdulescu G" first="Gabriela" last="Surdulescu">Gabriela Surdulescu</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Swaminathan, Ramasamyiyer" sort="Swaminathan, Ramasamyiyer" uniqKey="Swaminathan R" first="Ramasamyiyer" last="Swaminathan">Ramasamyiyer Swaminathan</name><affiliation wicri:level="3"><nlm:aff id="aff2"><addr-line>Chemical Pathology, Guy's and St Thomas' Hospitals Trust, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Chemical Pathology, Guy's and St Thomas' Hospitals Trust, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Spector, Tim" sort="Spector, Tim" uniqKey="Spector T" first="Tim" last="Spector">Tim Spector</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Ahmadi, Kourosh R" sort="Ahmadi, Kourosh R" uniqKey="Ahmadi K" first="Kourosh R." last="Ahmadi">Kourosh R. Ahmadi</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom</addr-line></nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Twin Research and Genetic Epidemiology, King's College London, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The liver function test (LFT) is among the most commonly used clinical investigations to assess hepatic function, severity of liver diseases and the effect of therapies, as well as to detect drug-induced liver injury (DILI).</p></sec><sec><title>Aims</title><p>To determine the relative contribution of genetic and environmental factors as well as test and quantify the effects of sex, age, BMI and alcohol consumption to variation in liver function test proteins - including alanine amino transaminase (ALT), Albumin, gamma glutamyl transpeptidase (GGT), total bilirubin, total protein, total globulin, aspartate transaminase (AST), and alkaline phosphotase (ALP) - using the classical twin model.</p></sec><sec sec-type="methods"><title>Methods</title><p>Blood samples were collected from a total of 5380 twin pairs from the TwinsUK registry. We measured the expression levels of major proteins associated with the LFT, calculated BMI from measured weight and height and questionnaires were completed for alcohol consumption by the twins. The relative contribution of genetic and environmental factors to variation in the LFT proteins was assessed and quantified using a variance components model fitting approach.</p></sec><sec><title>Results</title><p>Our results show that (1) variation in all the LFTs has a significant heritable basis (h<sup>2</sup> ranging from 20% to 77%); (2) other than GGT, the LFTs are all affected to some extent by common environmental factors (c<sup>2</sup> ranging from 24% to 54%); and (3) a small but significant proportion of the variation in the LFTs was due to confounding effects of age, sex, BMI, and alcohol use.</p></sec><sec><title>Conclusions</title><p>Variation in the LFT proteins is under significant genetic and common environmental control although sex, alcohol use, age and BMI also contribute significantly to inter-individual variation in the LFT proteins. Understanding the underlying genetic contribution of liver function tests may help the interpretation of their results and explain wide variation among individuals.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Rahmioglu, Nilufer" sort="Rahmioglu, Nilufer" uniqKey="Rahmioglu N" first="Nilufer" last="Rahmioglu">Nilufer Rahmioglu</name></region><name sortKey="Ahmadi, Kourosh R" sort="Ahmadi, Kourosh R" uniqKey="Ahmadi K" first="Kourosh R." last="Ahmadi">Kourosh R. Ahmadi</name><name sortKey="Andrew, Toby" sort="Andrew, Toby" uniqKey="Andrew T" first="Toby" last="Andrew">Toby Andrew</name><name sortKey="Cherkas, Lynn" sort="Cherkas, Lynn" uniqKey="Cherkas L" first="Lynn" last="Cherkas">Lynn Cherkas</name><name sortKey="Spector, Tim" sort="Spector, Tim" uniqKey="Spector T" first="Tim" last="Spector">Tim Spector</name><name sortKey="Surdulescu, Gabriela" sort="Surdulescu, Gabriela" uniqKey="Surdulescu G" first="Gabriela" last="Surdulescu">Gabriela Surdulescu</name><name sortKey="Swaminathan, Ramasamyiyer" sort="Swaminathan, Ramasamyiyer" uniqKey="Swaminathan R" first="Ramasamyiyer" last="Swaminathan">Ramasamyiyer Swaminathan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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