HLA-associated genetic resistance and susceptibility to type I diabetes in French North Africans and French natives

The distribution of human leukocyte antigen (HLA)‐DRB1–DQA1–DQB1 haplotypes was analyzed separately in two distinct French ethnic groups with type I diabetes (T1D), i.e. French North African migrants (n= 64, mean age at diagnosis = 8.25 years) and ancient French natives (n= 60, mean age at diagnosis = 7.42 years). HLA associations were determined by calculating odds ratios (ORs) between patients and two ethnic‐matched control populations. Results show highly similar ORs for the conservative DRB1*0301–DQA1*0501–DQB1*0201 haplotype of susceptibility (OR: 3.22 and 3.93 in migrants and natives, respectively) and the DRB1*1501–DQA1*0102–DQB1*0602 haplotype of resistance (OR: 0.05 and 0.03, respectively). In contrast, among the more variable DRB1*04–DQB1*0302 haplotypes of susceptibility, the DRB1*0402 (OR: 3.10 and 32.84) and 0405 (OR: 5.90 and 16.25, respectively) were associated with T1D in migrants and natives, whereas an increase of DRB1*0401, a rare allele in migrants, was significant in natives only. Also, among the DRB1*11–DQA1*0505–DQB1*0301 haplotypes of resistance, the OR observed for DRB1*1104–DQA1*0505–DQB1*0301, common in migrants, was lower (OR: 0.08) than for DRB1*1101–DQA1*0505–DQB1*0301 (OR: 0.32), common in natives. How DRB1*11 subtypes might affect differently the risk conferred by DQA1*0505–DQB1*0301 will be discussed.