HLA class I and II alleles are associated with microvascular complications of type 1 diabetes

Although HLA alleles are associated with type 1 diabetes, association with microvascular complications remains controversial. We tested HLA association with complications in multiplex type 1 diabetes families. Probands from 425 type I diabetes families from the Human Biological Data Interchange (HBDI) collection were analyzed. The frequencies of specific HLA alleles in patients with complications were compared with the frequencies in complications-free patients. The complications we examined were: retinopathy, neuropathy, and nephropathy. We used logistic regression models with covariates to estimate odds ratios. We found that the DRB1*03:01 allele is a protective factor for complications (OR = 0.58; p = 0.03), as is the DQA1*05:01-DQB1*02:01 haplotype found in linkage disequilibrium with DRB1*03:01 (OR = 0.59; p = 0.031). The DRB1*04:01 allele showed no evidence of association (OR = 1.13; p = 0.624), although DRB1*04:01 showed suggestive evidence when the carriers of the protective DRB1*03:01 were removed from the analysis. The class II DQA1*03:01-DQB1*03:02 haplotype was not associated with complications, but the class I allele B*39:06 (OR = 3.27; p = 0.008) suggested a strong positive association with complications. Our results show that in type 1 diabetes patients, specific HLA alleles may be involved in susceptibility to, or protection from, microvascular complications. (C) 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.