Repository series · ncbi-prjeb43273

rdance of type 1 diabetes in families with HLA-DR4 and HLA-DR3 haplotypes from the United Arab Emirates

The classical class II haplotypes of the Major Histocompatibility Complex (MHC) that are associated with Type 1 diabetes (T1D) were identified in five families from the United Arab Emirates (UAE). Using genomic DNA, Segregation analysis were performed on 5 families with the disease, 3 with one offspring and 2 with 2 children diagnosed with T1D. Three HLA-DR4 haplotypes were identified: HLA-DRB1*04:01:01:NC-HLA-DQB1*03:02:01:01; HLA- DRB1*04:02:01-HLA-DQB1*03:02:01; HLA-DRB1*04:05:01-HLA-DQB1*02:02:01:02, all previously identified in studies of the Arabian population. There was on HLA-DR3 haplotype, namely HLA*03:01:01:NC-HLA-DQB1*02:01:01. Results: In the 10 parents from the 5 families, 9 had at least one HLA-DR4 and/ HLA-DR3 haplotype which potentially predisposes them to T1D. Of these 9 parents, 3 were heterozygous for HLA-DR4 / HLA-DR3 and one was homozygous for HLA-DR3. At face value these parents should have succumbed to T1D but have not. The youngest parent was born in the 1980s. In two families, the HLA-DR and HLA-DQ genotypes were identical between the parent; who was unaffected; and offspring who were diagnosed with T1D at a young age. Although the genotypes were identical, the haplotypes were different, albeit marked by the same alleles. Epistatic interaction between candidate genes within and/or separate from the MHC could be at play. Another possible explanation lies in the possibility of an environmental trigger. The socioeconomic condition of the UAE changed rapidly in the 1980s, and dramatic changes to diet, healthcare, sanitation and lifestyle, factors that have been suggested in studies elsewhere.