Contribution of Selective HLA-DRB1/DQB1 Alleles and Haplotypes to the Genetic Susceptibility of Type 1 Diabetes among Lebanese and Bahraini Arabs

Abstract

Human leukocyte antigen (HLA) class II genes contribute to the genetic susceptibility of type 1 diabetes (T1D), and both susceptible and protective alleles were implicated with its pathogenesis, which varies among various ethnic/racial groups. This study investigated the heterogeneity in HLA class II haplotypes distribution among Bahraini and Lebanese T1D patients. This was a cross-sectional retrospective study. The study was conducted at primary care private and public health centers. Subjects comprised 126 T1D patients and 126 healthy controls from Bahrain and 78 Lebanese T1D patients and 111 control subjects. There were no interventions. Although Lebanese and Bahraini patients share DRB1*030101, DQB1*0201 as susceptible and DRB1*100101 and DQB1*030101 as protective alleles, DRB1*040101 was an additional susceptible allele in Bahraini patients, and DRB1*130701 and DQB1*050101 were additional susceptible and protective alleles in Lebanese, respectively. DRB1*030101-DQB1*0201 was susceptible, whereas DRB1*070101-DQB1*0201 and DRB1*110101-DQB1*030101 were protective haplotypes in Bahraini and Lebanese. DRB1*040101-DQB1*0302 and DRB1*040101-DQB1*050101 displayed different associations: they were protective in Lebanese but susceptible or neutral among Bahrainis. Whereas the frequency of homozygous DRB1*03011-DQB1*0201 was higher in Bahraini and to a lesser extent Lebanese patients, homozygous DRB1*110101-DQB1*030101 was significantly more frequent in Lebanese but not Bahraini controls, whereas DRB1*030101-DQB1*0201/DRB1*040101-DQB1*0201 was the major genotype among Bahraini patients but not Lebanese subjects in whom it was present at very low frequencies. In view of these differences between Bahraini and Lebanese, this demonstrates that the contribution of HLA class II to the genetic susceptibility to T1D must be evaluated with regard to specific HLA haplotypes and also ethnic origin and racial background.