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Race-specific type 1 diabetes risk of HLA-DR7 haplotypes.

Abstract
The aim of this study was to test the hypothesis that closely related human leukocyte antigen (HLA) haplotypes containing the DRB1*07:01 gene ['DR7' (DRB1*07:01-DQA1*02:01-DQB1*02:01g or DRB1*07:01-DQA1*03:01-DQB1*02:01g) haplotypes] derived from European and African populations differ in their genetic susceptibility for type 1 diabetes (T1D) depending on the DQ-α molecule present. A combined total of 98 African American T1D patients from the Type 1 Diabetes Genetics Consortium and from Children's Hospital and Research Center Oakland were genotyped for the HLA class II loci DRB1, DQA1, and DQB1. DNA samples extracted from newborn blood spot cards from African Americans born in California (n = 947) were used as a population-based control group. Among African American cases, the European-derived DRB1*07:01-DQA1*02:01-DQB1*02:01g haplotype was protective for T1D risk (odds ratio (OR) = 0.34; 95% confidence interval (CI) 0.14-0.78; P < 0.011), but the African-derived DRB1*07:01-DQA1*03:01-DQB1*02:01g haplotype increased T1D risk (OR = 3.96; 95% CI 1.94-8.08; P < 5.5E-05). The effect of DRB1*07:01-DQB1*02:01g on T1D susceptibility depends on the DQA1 allele. DRB1*07:01-DQA1*02:01-DQB1*02:01g is protective for T1D; however, the presence of DQA1*03:01 on the DRB1*07:01-DQB1*02:01g haplotype not only renders the DR7 haplotype not protective but also creates a haplotype with significant T1D risk. These data underscore the importance of assessing genetic effects within ethnic context.
AuthorsJ A Noble, J Johnson, J A Lane, A M Valdes
JournalTissue antigens (Tissue Antigens) Vol. 78 Issue 5 Pg. 348-51 (Nov 2011) ISSN: 1399-0039 [Electronic] England
PMID21988721 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright© 2011 John Wiley & Sons A/S.
Chemical References
  • HLA-DQ Antigens
  • HLA-DR7 Antigen
Topics
  • Adolescent
  • Black People (ethnology, genetics)
  • Child
  • Diabetes Mellitus, Type 1 (genetics, immunology)
  • Genetic Predisposition to Disease
  • HLA-DQ Antigens (genetics, immunology)
  • HLA-DR7 Antigen (genetics, immunology)
  • Haplotypes
  • Humans
  • Male
  • Risk Factors
  • Young Adult

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