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Genetics of the HLA Region in the Prediction of Type 1 Diabetes
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Genetics of the HLA Region in the Prediction of Type 1 Diabetes
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Journal Article
Genetics of the HLA Region in the Prediction of Type 1 Diabetes
2011
Overview
Type 1 diabetes (T1D) is one of the most widely studied complex genetic disorders, and the genes in HLA are reported to account for approximately 40–50% of the familial aggregation of T1D. The major genetic determinants of this disease are polymorphisms of class II HLA genes encoding DQ and DR. The DR-DQ haplotypes conferring the highest risk are
DRB1
*03:01-
DQA1
*05:01-
DQB1
*02:01 (abbreviated “DR3”) and
DRB1
*04:01/02/04/05/08-
DQA1
*03:01-
DQB1
*03:02/04 (or
DQB1
*02; abbreviated “DR4”). The risk is much higher for the heterozygote formed by these two haplotypes (OR = 16.59; 95% CI, 13.7–20.1) than for either of the homozygotes (DR3/DR3, OR = 6.32; 95% CI, 5.12–7.80; DR4/DR4, OR = 5.68; 95% CI, 3.91). In addition, some haplotypes confer strong protection from disease, such as
DRB1
*15:01-
DQA1
*01:02-
DQB1
*06:02 (abbreviated “DR2”; OR = 0.03; 95% CI, 0.01–0.07). After adjusting for the genetic correlation with DR and DQ, significant associations can be seen for HLA class II
DPB1
alleles, in particular,
DPB1
*04:02,
DPB1
*03:01, and
DPB1
*02:02. Outside of the class II region, the strongest susceptibility is conferred by class I allele B*39:06 (OR =10.31; 95% CI, 4.21–25.1) and other
HLA-B
alleles. In addition, several loci in the class III region are reported to be associated with T1D, as are some loci telomeric to class I. Not surprisingly, current approaches for the prediction of T1D in screening studies take advantage of genotyping HLA-DR and HLA-DQ loci, which is then combined with family history and screening for autoantibodies directed against islet-cell antigens. Inclusion of additional moderate HLA risk haplotypes may help identify the majority of children with T1D before the onset of the disease.
Publisher
Current Science Inc
