HLA DPA1, DPB1 Alleles and Haplotypes Contribute to the Risk Associated With Type 1 Diabetes Analysis of the Type 1 Diabetes Genetics Consortium Families

被引：60

作者：

Varney, Michael D. ^{[1
]}

Valdes, Ana Maria ^{[2
]}

Carlson, Joyce A. ^{[3
]}

Noble, Janelle A. ^{[4
]}

Tait, Brian D. ^{[1
]}

Bonella, Persia ^{[4
]}

Lavant, Eva ^{[3
]}

Fear, Anna Lisa ^{[4
]}

Louey, Anthony ^{[1
]}

Moonsamy, Priscilla ^{[5
]}

Mychaleckyj, Josyf C. ^{[6
]}

Erlich, Henry ^{[4
,5
]}

机构：

[1] Australian Red Cross Blood Serv, Victorian Transplantat & Immunogenet Serv, Melbourne, Vic, Australia

[2] Kings Coll London, Dept Twin Res, London WC2R 2LS, England

[3] Malmo Univ Hosp, Malmo, Sweden

[4] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA

[5] Roche Mol Syst, Alameda, CA USA

[6] Univ Virginia, Publ Hlth Sci Bioinformat & Genet Ctr Publ Hlth G, Charlottesville, VA USA

来源：

DIABETES | 2010年 / 59卷 / 08期

关键词：

HUMAN-LEUKOCYTE ANTIGEN; PEPTIDE-BINDING-SPECIFICITY; CHRONIC BERYLLIUM DISEASE; CLASS-II ALLELES; RISING INCIDENCE; CRUCIAL ROLE; DR ALLELES; SUSCEPTIBILITY; MELLITUS; POLYMORPHISM;

D O I：

10.2337/db09-0680

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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

引用

页码：2055 / 2062

页数：8

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