期刊
DIABETES
卷 61, 期 11, 页码 3012-3017出版社
AMER DIABETES ASSOC
DOI: 10.2337/db11-1694
关键词
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资金
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases
- National Human Genome Research Institute
- National Institute of Child Health and Human Development
- Juvenile Diabetes Research Foundation International (JDRF)
- Wellcome Trust (WT) [076113]
- National Institute for Health Research Cambridge Biomedical Centre
- WT Strategic Award [079895]
- JDRF
- [U01 DK-062418]
- British Heart Foundation [RG/08/014/24067] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10275] Funding Source: researchfish
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 x 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 X 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. Diabetes 61:3012-3017, 2012
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