HLA haplotypes in families with type 1 diabetes

Background: Inherited susceptibility to type 1 diabetes is partially determ ined by HLA genes. HLA-DQA1 and DQB1 alleles have been chosen as the most s ensitive susceptibility markers. Family studies are a good method to establ ish specific relationship between type 1 diabetes and specific haplotypes a s risk markers for the disease. Aim: To analyse the role of class II HLA mo lecules and the distribution of haplotypes in the genetic predisposition to type 1 diabetes in Chilean families. Materials and methods: Twelve family groups constituted by 58 individuals were studied. Fourteen children (10 ma le) less than 15 years old with diabetes and their family members were incl uded. The allele and haplotype frequency of the population was determined i n 74 unrelated healthy children. Results: Risk haplotypes such as HLA-DR3/D QB1*0201/DQA1*0501 and HLA-DQB10302/DQA1*0501 were more common among diabet ic patients and compared to the haplotypes described in other Caucasian pop ulations. Meanwhile, protective haplotypes found in relatives without diabe tes, such as HLA-DR2/DQB1*0301/DQA1*0301 and HLA-DR8/DQB1*0402/DQA1*0301, w ere absent in children with diabetes. Conclusions: The general pattern of n eutral or protective haplotypes, found with higher frequency in non diabeti c individuals, indicates that their presence could confer protection agains t the disease, with a higher effect over those haplotypes associated to the disease.