AustralieFrV1, Main, Exploration, bibRecord, 005C76

Evidence of Gene-Gene Interaction and Age-at-Diagnosis Effects in Type 1 Diabetes

Identifieur interne : 005C76 ( Main/Exploration ); précédent : 005C75; suivant : 005C77

Evidence of Gene-Gene Interaction and Age-at-Diagnosis Effects in Type 1 Diabetes

Auteurs : Joanna M. M. Howson [Royaume-Uni] ; Jason D. Cooper [Royaume-Uni] ; Deborah J. Smyth [Royaume-Uni] ; Neil M. Walker [Royaume-Uni] ; Helen Stevens [Royaume-Uni] ; Jin-Xiong She [États-Unis] ; George S. Eisenbarth [États-Unis] ; Marian Rewers [États-Unis] ; John A. Todd [Royaume-Uni] ; Beena Akolkar [États-Unis] ; Patrick Concannon [États-Unis] ; Henry A. Erlich [États-Unis] ; Cecile Julier [France] ; GRANT-MORAHAN [Australie] ; J Rn Nerup [Danemark] ; Concepcion Nierras [États-Unis] ; Flemming Pociot [Danemark] ; Stephen S. Rich [États-Unis]

Source :

Diabetes : (New York, NY) [ 0012-1797 ] ; 2012.

RBID : Pascal:13-0035332

Descripteurs français

Pascal (Inist)
- Gène, Interaction, Age, Diagnostic, Diabète de type 1.

English descriptors

KwdEn :
- Age, Diagnosis, Gene, Interaction, Type 1 diabetes.

Abstract

The common genetic loci that independently influence the risk of type 1 diabetes have largely been determined. Their interactions with age-at-diagnosis of type 1 diabetes, sex, or the major susceptibility locus, HLA class II, remain mostly unexplored. A large collection of more than 14,866 type 1 diabetes samples (6,750 British diabetic individuals and 8,116 affected family samples of European descent) were genotyped at 38 confirmed type 1 diabetes-associated non-HLA regions and used to test for interaction of association with age-at-diagnosis, sex, and HLA class II genotypes using regression models. The alleles that confer susceptibility to type 1 diabetes at interleukin-2 (IL-2), IL2/4q27 (rs2069763) and renalase, FAD-dependent amine oxidase (RNLS)/10q23.31 (rs10509540), were associated with a lower age-at-diagnosis (P = 4.6 × 10^-6 and 2.5 x 10^-5, respectively). For both loci, individuals carrying the susceptible homozygous genotype were, on average, 7.2 months younger at diagnosis than those carrying the protective homozygous genotypes. In addition to protein tyrosine phosphatase nonreceptor type 22 (PTPN22), evidence of statistical interaction between HLA class II genotypes and rs3087243 at cytotoxic T-lymphocyte antigen 4 (CTLA4)/ 2q33.2 was obtained (P = 7.90 × 10^-5). No evidence of differential risk by sex was obtained at any loci (P ≥ 0.01). Statistical interaction effects can be detected in type 1 diabetes although they provide a relatively small contribution to our understanding of the familial clustering of the disease. J.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478521

Affiliations:

Le document en format XML

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<sZ>8 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rewers, Marian" sort="Rewers, Marian" uniqKey="Rewers M" first="Marian" last="Rewers">Marian Rewers</name>
<affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine</s1>
<s2>Aurora, Colorado</s2>
<s3>USA</s3>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Colorado</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Todd, John A" sort="Todd, John A" uniqKey="Todd J" first="John A." last="Todd">John A. Todd</name>
<affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, Department of Medical Genetics, University of Cambridge</s1>
<s2>Cambridge</s2>
<s3>GBR</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Royaume-Uni</country>
<placeName><settlement type="city">Cambridge</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Angleterre de l'Est</region>
</placeName>
<orgName type="university">Université de Cambridge</orgName>
</affiliation>
</author>
<author><name sortKey="Akolkar, Beena" sort="Akolkar, Beena" uniqKey="Akolkar B" first="Beena" last="Akolkar">Beena Akolkar</name>
<affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Division of Diabetes, Endocrinology, and Metabolic Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health</s1>
<s2>Bethesda, Maryland</s2>
<s3>USA</s3>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Concannon, Patrick" sort="Concannon, Patrick" uniqKey="Concannon P" first="Patrick" last="Concannon">Patrick Concannon</name>
<affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Biochemistry and Molecular Genetics, University of Virginia</s1>
<s2>Charlottesville, Virginia</s2>
<s3>USA</s3>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Center for Public Health Genomics, University of Virginia</s1>
<s2>Charlottesville, Virginia</s2>
<s3>USA</s3>
<sZ>11 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Erlich, Henry A" sort="Erlich, Henry A" uniqKey="Erlich H" first="Henry A." last="Erlich">Henry A. Erlich</name>
<affiliation wicri:level="2"><inist:fA14 i1="07"><s1>Roche Molecular Systems</s1>
<s2>Pleasanton, California</s2>
<s3>USA</s3>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Julier, Cecile" sort="Julier, Cecile" uniqKey="Julier C" first="Cecile" last="Julier">Cecile Julier</name>
<affiliation wicri:level="3"><inist:fA14 i1="08"><s1>University Paris 7 Denis-Diderot</s1>
<s2>Paris</s2>
<s3>FRA</s3>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Grant Morahan" sort="Grant Morahan" uniqKey="Grant Morahan" last="Grant-Morahan">GRANT-MORAHAN</name>
<affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Centre for Diabetes Research, the Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia</s1>
<s2>Perth, Western Australia</s2>
<s3>AUS</s3>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>Australie</country>
<wicri:noRegion>Perth, Western Australia</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nerup, J Rn" sort="Nerup, J Rn" uniqKey="Nerup J" first="J Rn" last="Nerup">J Rn Nerup</name>
<affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Steno Diabetes Center and Hagedorn Research Institute</s1>
<s2>Gentofte</s2>
<s3>DNK</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Danemark</country>
<wicri:noRegion>Steno Diabetes Center and Hagedorn Research Institute</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nierras, Concepcion" sort="Nierras, Concepcion" uniqKey="Nierras C" first="Concepcion" last="Nierras">Concepcion Nierras</name>
<affiliation wicri:level="2"><inist:fA14 i1="11"><s1>Juvenile Diabetes Research Foundation</s1>
<s2>New York, New York</s2>
<s3>USA</s3>
<sZ>16 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">État de New York</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pociot, Flemming" sort="Pociot, Flemming" uniqKey="Pociot F" first="Flemming" last="Pociot">Flemming Pociot</name>
<affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Glostrup Research Institute, Glostrup Hospital</s1>
<s2>Glostrup</s2>
<s3>DNK</s3>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>Danemark</country>
<wicri:noRegion>Glostrup</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Rich, Stephen S" sort="Rich, Stephen S" uniqKey="Rich S" first="Stephen S." last="Rich">Stephen S. Rich</name>
<affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Center for Public Health Genomics, University of Virginia</s1>
<s2>Charlottesville, Virginia</s2>
<s3>USA</s3>
<sZ>11 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="13"><s1>Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia</s1>
<s2>Charlottesville, Virginia</s2>
<s3>USA</s3>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Virginie</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Diabetes : (New York, NY)</title>
<title level="j" type="abbreviated">Diabetes : (N.Y. NY)</title>
<idno type="ISSN">0012-1797</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Diabetes : (New York, NY)</title>
<title level="j" type="abbreviated">Diabetes : (N.Y. NY)</title>
<idno type="ISSN">0012-1797</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Age</term>
<term>Diagnosis</term>
<term>Gene</term>
<term>Interaction</term>
<term>Type 1 diabetes</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Gène</term>
<term>Interaction</term>
<term>Age</term>
<term>Diagnostic</term>
<term>Diabète de type 1</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">The common genetic loci that independently influence the risk of type 1 diabetes have largely been determined. Their interactions with age-at-diagnosis of type 1 diabetes, sex, or the major susceptibility locus, HLA class II, remain mostly unexplored. A large collection of more than 14,866 type 1 diabetes samples (6,750 British diabetic individuals and 8,116 affected family samples of European descent) were genotyped at 38 confirmed type 1 diabetes-associated non-HLA regions and used to test for interaction of association with age-at-diagnosis, sex, and HLA class II genotypes using regression models. The alleles that confer susceptibility to type 1 diabetes at interleukin-2 (IL-2), IL2/4q27 (rs2069763) and renalase, FAD-dependent amine oxidase (RNLS)/10q23.31 (rs10509540), were associated with a lower age-at-diagnosis (P = 4.6 × 10<sup>-6</sup>
 and 2.5 x 10<sup>-5</sup>
, respectively). For both loci, individuals carrying the susceptible homozygous genotype were, on average, 7.2 months younger at diagnosis than those carrying the protective homozygous genotypes. In addition to protein tyrosine phosphatase nonreceptor type 22 (PTPN22), evidence of statistical interaction between HLA class II genotypes and rs3087243 at cytotoxic T-lymphocyte antigen 4 (CTLA4)/ 2q33.2 was obtained (P = 7.90 × 10<sup>-5</sup>
). No evidence of differential risk by sex was obtained at any loci (P ≥ 0.01). Statistical interaction effects can be detected in type 1 diabetes although they provide a relatively small contribution to our understanding of the familial clustering of the disease. J.</div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>Danemark</li>
<li>France</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Angleterre de l'Est</li>
<li>Californie</li>
<li>Colorado</li>
<li>Géorgie (États-Unis)</li>
<li>Maryland</li>
<li>Virginie</li>
<li>État de New York</li>
<li>Île-de-France</li>
</region>
<settlement><li>Cambridge</li>
<li>Paris</li>
</settlement>
<orgName><li>Université de Cambridge</li>
</orgName>
</list>
<tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Howson, Joanna M M" sort="Howson, Joanna M M" uniqKey="Howson J" first="Joanna M. M." last="Howson">Joanna M. M. Howson</name>
</region>
<name sortKey="Cooper, Jason D" sort="Cooper, Jason D" uniqKey="Cooper J" first="Jason D." last="Cooper">Jason D. Cooper</name>
<name sortKey="Smyth, Deborah J" sort="Smyth, Deborah J" uniqKey="Smyth D" first="Deborah J." last="Smyth">Deborah J. Smyth</name>
<name sortKey="Stevens, Helen" sort="Stevens, Helen" uniqKey="Stevens H" first="Helen" last="Stevens">Helen Stevens</name>
<name sortKey="Todd, John A" sort="Todd, John A" uniqKey="Todd J" first="John A." last="Todd">John A. Todd</name>
<name sortKey="Walker, Neil M" sort="Walker, Neil M" uniqKey="Walker N" first="Neil M." last="Walker">Neil M. Walker</name>
</country>
<country name="États-Unis"><region name="Géorgie (États-Unis)"><name sortKey="She, Jin Xiong" sort="She, Jin Xiong" uniqKey="She J" first="Jin-Xiong" last="She">Jin-Xiong She</name>
</region>
<name sortKey="Akolkar, Beena" sort="Akolkar, Beena" uniqKey="Akolkar B" first="Beena" last="Akolkar">Beena Akolkar</name>
<name sortKey="Concannon, Patrick" sort="Concannon, Patrick" uniqKey="Concannon P" first="Patrick" last="Concannon">Patrick Concannon</name>
<name sortKey="Concannon, Patrick" sort="Concannon, Patrick" uniqKey="Concannon P" first="Patrick" last="Concannon">Patrick Concannon</name>
<name sortKey="Eisenbarth, George S" sort="Eisenbarth, George S" uniqKey="Eisenbarth G" first="George S." last="Eisenbarth">George S. Eisenbarth</name>
<name sortKey="Erlich, Henry A" sort="Erlich, Henry A" uniqKey="Erlich H" first="Henry A." last="Erlich">Henry A. Erlich</name>
<name sortKey="Nierras, Concepcion" sort="Nierras, Concepcion" uniqKey="Nierras C" first="Concepcion" last="Nierras">Concepcion Nierras</name>
<name sortKey="Rewers, Marian" sort="Rewers, Marian" uniqKey="Rewers M" first="Marian" last="Rewers">Marian Rewers</name>
<name sortKey="Rich, Stephen S" sort="Rich, Stephen S" uniqKey="Rich S" first="Stephen S." last="Rich">Stephen S. Rich</name>
<name sortKey="Rich, Stephen S" sort="Rich, Stephen S" uniqKey="Rich S" first="Stephen S." last="Rich">Stephen S. Rich</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Julier, Cecile" sort="Julier, Cecile" uniqKey="Julier C" first="Cecile" last="Julier">Cecile Julier</name>
</region>
</country>
<country name="Australie"><noRegion><name sortKey="Grant Morahan" sort="Grant Morahan" uniqKey="Grant Morahan" last="Grant-Morahan">GRANT-MORAHAN</name>
</noRegion>
</country>
<country name="Danemark"><noRegion><name sortKey="Nerup, J Rn" sort="Nerup, J Rn" uniqKey="Nerup J" first="J Rn" last="Nerup">J Rn Nerup</name>
</noRegion>
<name sortKey="Pociot, Flemming" sort="Pociot, Flemming" uniqKey="Pociot F" first="Flemming" last="Pociot">Flemming Pociot</name>
</country>
</tree>
</affiliations>
</record>

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Evidence of Gene-Gene Interaction and Age-at-Diagnosis Effects in Type 1 Diabetes

Evidence of Gene-Gene Interaction and Age-at-Diagnosis Effects in Type 1 Diabetes

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