HLA haplotypes in families with type 1 diabetes

Inherited susceptibility to type 1 diabetes is partially determined by HLA genes. HLA-DQA1 and DQB1 alleles have been chosen as the most sensitive susceptibility markers. Family studies are a good method to establish specific relationship between type 1 diabetes and specific haplotypes as risk markers for the disease. To analyse the role of class II HLA molecules and the distribution of haplotypes in the genetic predisposition to type 1 diabetes in Chilean families. Twelve family groups constituted by 58 individuals were studied. Fourteen children (10 male) less than 15 years old with diabetes and their family members were included. The allele and haplotype frequency of the population was determined in 74 unrelated healthy children. Risk haplotypes such as HLA-DR3/DQB1*0201/DQA1*0501 and HLA-DQB10302/DQA1*0501 were more common among diabetic patients and comparable to the haplotypes described in other Caucasian populations. Meanwhile, protective haplotypes found in relatives without diabetes, such as HLA-DR2/DQB1*0301/DQA1*0301 and HLA-DR8/DQB1*0402/DQA1*0301, were absent in children with diabetes. The general pattern of neutral or protective haplotypes, found with higher frequency in non diabetic individuals, indicates that their presence could confer protection against the disease, with a higher effect over those haplotypes associated to the disease.