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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DOI：
10.2337/db11-1694
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发表时间：
2012-11
期刊：
影响因子：
7.7
通讯作者：
Type 1 Diabetes Genetics Consortium
中科院分区：
文献类型：
--
作者：
Howson JM;Cooper JD;Smyth DJ;Walker NM;Stevens H;She JX;Eisenbarth GS;Rewers M;Todd JA;Akolkar B;Concannon P;Erlich HA;Julier C;Morahan G;Nerup J;Nierras C;Pociot F;Rich SS;Type 1 Diabetes Genetics Consortium
独立影响1型糖尿病风险的常见遗传位点已在很大程度上确定。它们与1型糖尿病诊断时的年龄、性别或主要易感基因位点HLA II类的相互作用大多未被探索。对超过14，866份1型糖尿病样本（6，750名英国糖尿病患者和8，116名欧洲血统的受影响家族样本）进行了38个确认的1型糖尿病相关非HLA区域的基因分型，并使用回归模型测试与诊断时年龄，性别和HLA II类基因型相关的相互作用。在白细胞介素2（IL-2），IL 2/4 q27（rs 2069763）和肾酶，FAD依赖性胺氧化酶（RNLS）/10q23.31（rs 10509540）上赋予1型糖尿病易感性的等位基因与较低的诊断年龄相关（P = 4.6 × 10−6和2.5 × 10−5，分别）。对于这两个位点，携带易感纯合基因型的个体在诊断时平均比携带保护性纯合基因型的个体年轻7.2个月。除了蛋白酪氨酸磷酸酶非受体22（PTPN 22），还获得了HLA II类基因型与细胞毒性T淋巴细胞抗原4（CTLA 4）/2q33.2处rs3087243之间统计学相互作用的证据（P = 7.90 × 10−5）。在任何位点均未获得性别差异风险的证据（P ≥ 0.01）。统计相互作用的影响，可以检测到1型糖尿病，虽然他们提供了一个相对较小的贡献，我们的理解的家族聚集性疾病。
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 × 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.
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影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
影响因子：
8.2
作者：
Bjornvold, M.;Undlien, D. E.;Joner, G.;Dahl-Jorgensen, K.;Njolstad, P. R.;Akselsen, H. E.;Gervin, K.;Ronningen, K. S.;Stene, L. C.
通讯作者：
Stene, L. C.
影响因子：
0.9
作者：
Malyszko, J.;Zbroch, E.;Mysliwiec, M.
通讯作者：
Mysliwiec, M.
影响因子：
9.8
作者：
Bugawan, TL;Mirel, DB;Erlich, HA
通讯作者：
Erlich, HA
影响因子：
2.1
作者：
So, Hon-Cheong;Gui, Allen H. S.;Sham, Pak C.
通讯作者：
Sham, Pak C.