Genetic variation within the HLA class III influences T1D susceptibility conferred by high-risk HLA haplotypes.

ABSTRACT: Human leukocyte antigen (HLA) class II DRB1 and DQB1 represent the major type I diabetes (T1D) genetic susceptibility loci; however, other genes in the HLA region are also involved in T1D risk. We analyzed 1411 pedigrees (2865 affected individuals) from the type I diabetes genetics consortium genotyped for HLA classical loci and for 12 single-nucleotide polymorphisms (SNPs) in the class III region previously shown to be associated with T1D in a subset of 886 pedigrees. Using the transmission disequilibrium test, we compared the proportion of SNP alleles transmitted from within the high-risk DR3 and DR4 haplotypes to affected offspring. Markers rs4151659 (mapping to CFB) and rs7762619 (mapping 5' of LTA) were the most strongly associated with T1D on DR3 (P=1.2 x 10(-9) and P=2 x 10(-12), re

SUBMITTER: Valdes AM 

PROVIDER: S-EPMC2858242 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature