期刊
DIABETES
卷 59, 期 8, 页码 2055-2062出版社
AMER DIABETES ASSOC
DOI: 10.2337/db09-0680
关键词
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资金
- Type 1 Diabetes Genetics Consortium
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases (NIAID), National Human Genome Research Institute (NHGRI), National Institute of Child Health and Human Development (NICHD)
- Juvenile Diabetes Research Foundation International (JDRF) [U01 DK062418]
OBJECTIVE-To determine the relative risk associated with DPA1 and DPB1 alleles and haplotypes in type I diabetes. RESEARCH DESIGN AND METHODS-The frequency of DPA1 and DPB1 alleles and haplotypes in type I diabetic patients was compared to the family based control frequency in 1,771 families directly and conditional on FILA (B)-DRB1-DQA1-DQB1 linkage disequilibrium. A relative predispositional analysis (RPA) was performed in the presence or absence of the primary HLA DR-DQ associations and the contribution of DP haplotype to individual DR-DQ haplotype risks examined. RESULTS-Eight DPAI and thirty-eight DPB1 alleles forming seventy-four DPA1-DPB1 haplotypes were observed, nineteen DPB1 alleles were associated with multiple DPA1 alleles Following both analyses, type I diabetes susceptibility was significantly associated with DPB1*0301 (DPA1*0103-DPB1*0301) and protection with DPB1*0402 (DPA1*0103-DPB1*0402) and DPA1*0103-DPB1*0101 but not DPA1*0201-DPB1*0101. In addition, DPB1*0202 (DPA1*0103-DPB1*0202) and DPB1*0201 (DPA1*0103-DPB1*0201) were significantly associated with susceptibility in the presence of the high risk and protective DR-DQ haplotypes Three associations (DPB1*0301, *0402, and *0202) remained statistically significant when only the extended HLA-A1-B8-DR3 haplotype was considered, suggesting that DPB1 alone may delineate the risk associated with this otherwise conserved haplotype CONCLUSIONS-HLA DP allelic and haplotypic diversity contributes significantly to the risk for type I diabetes; DPB1*0301 (DPA1*0103-DPB1*0301) is associated with susceptibility and DPB1*0402 (DPA1*0103-DPB1*0402) and DPA1*0103-DPB1*0101 with protection Additional evidence is presented for the susceptibility association of DPB1*0202 (DPA1*0103-DPB1*0202) and for a contributory role of individual amino acids and DPA1 or a gene in linkage disequilibrium in DR3-DPB1*0101 positive haplotypes Diabetes 59:2055-2062, 2010
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