Genetic association of type 1 diabetes in an Azerbaijanian population: the HLA-DQ, -DRB1*04, the insulin gene, and CTLA4

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Abstract
Little is known on the genetic susceptibility to type 1 diabetes mellitus (T1DM) in the nations of the former Soviet part of south-west Asia. The aim of the study was to characterize the genetic association of T1DM in the Azeri, the majority population of Azerbaijan. One hundred and sixty patients with childhood-onset T1DM, and 271 healthy unrelated controls were compared in a case-control study. All declared themselves as Azeri. The human leukocyte antigen (HLA)-DQB1, -DQA1 alelles, of DRB1*04 subtypes, and of insulin gene and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) single nucleotide polymorphisms were determined using polymerase chain reaction (PCR) techniques, the association was tested from cross-tabulations, and quantified using odds ratios (OR). In the non-HLA factors, analyses were also stratified according to the HLA-conferred risk. Risk for T1DM was associated with presence of the HLA-DQB1*02-DQA1*05, OR = 6.6 [95% confidence interval (CI) 4.3-10], the HLA-DQB1*0302-DQA1*03, OR = 3.9 (95% CI 2.6-6.0), and an unexpectedly high risk was observed for DQB1*0304, OR = 10.9, but the very wide CI (CI 95% 2.4-49) prompts careful interpretation. A negative association with diabetes was observed for the DQB1*0602, 0503, 0301, and 0601 alleles, as well as the DRB1*0403 subtype. A strong protection was also associated with the less frequent variant of the insulin gene (OR of the phenotypic positivity was 0.28, CI 95% 0.17-0.46), while the CTLA4 +49 A/G transition was not associated with T1DM. We bring the first report on both HLA, and non-HLA association of T1DM from the majority Azeri population of Azerbaijan.