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 1 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.