Investigation the role of gender on the HLA-DRB1 and -DQB1 association with type 1 diabetes mellitus in Iranian patients

ABSTRACT

Type 1 diabetes mellitus [T1D] is an autoimmune and multifactorial disorder. Subsequent analysis on human leukocyte antigen [HLA] region shows that HLA-DRB1 and -DQB1 genes have the strongest association with T1D. In this study, for the first time, we investigated the influence of gender on the HLA-DRB1 and -DQB1 association with type 1 diabetes mellitus in Iranian patients in order to determine gender dependent HLA heterogeneity in Iranian T1D patients. In this case control study, the HLA-DRB1 and -DQB1 typing were performed on 105 Iranian T1D patients and 100 healthy controls. The data were evaluated by using Fisher exact test. Our results indicate that DRB1*0401, DQB1*0302 alleles and DRB1*0401-DQB1*0302 haplotype were significantly more frequent in male T1D patients than females. Also, DRB1*0301, DRB1*1501, DQB1*0601 alleles, DQB1*0301/0501 genotype, DRB1*0301-DQB1*0201 and DRB1*1501-DQB1*0601 haplotypes were significantly higher in female T1D group than males. Furthermore, our results showed that DRB1*0401 and DQB1*0302 alleles were significantly more frequent in male T1D patients 1-5 years old at onset than females with similar condition. The DRB1*0301 allele and DRB1*0301-DQB1*0201 haplotype were significantly higher in female T1D patients 6-10 years old at onset than males with similar condition. The DRB1*1501 allele and DRB1*1501-DQB1*0601 haplotype were significantly more frequent in female T1D patients 16-20 years old at onset than males with similar condition. Our findings suggest that gender has a significant influence on the distribution of HLA-DR and -DQ alleles, genotypes and haplotypes. Also, distribution of the HLA-DRB1 and -DQB1 alleles, genotypes and haplotypes vary based on the gender of T1D patients in different age at onset