Is HLA the cause of the high incidence of type 1 diabetes in the Canary Islands? Results from the Type 1 Diabetes Genetics Consortium (T1DGC)

Abstract

Background and aims:The incidence of childhood-onset type 1 diabetes in the Canary Islands is the highest described so far in Spain, and one of the highest worldwide. Our aim was to assess high-risk and protective HLA haplotype distribution in the Canarian families included in the T1DGC, compared with the rest of SpainMaterials and methods:The T1DGC is an international effort to study the genetics and pathogenesis of type 1 diabetes. It included more than 3300 families with type 1 diabetes worldwide. Spain provided 149 of these families, of whom 42 were from the Canary Islands Tenerife and Gran Canaria. HLA was genotyped centrally in Malmö, Sweden, using a PCR-based, sequence-specific oligonucleotide probe system. A deterministic algorithm (alleHap) was developed in the environment R, to impute HLA haplotypes. Based on previous T1DGC results in Caucasian population, haplotypes DRB1*0405-DQA1*0301-DQB1*0302, DRB1*0401-DQA1*0301-DQB1*0302, DRB1*0301-DQA1*0501-DQB1*0201 and DRB1*0402-DQA1*0301-DQB1*0302 and DRB1*0404-DQA1*0301-DQB1*0302 were considered high-risk. DRB1*0701-DQA1*0201-DQB1*0303, DRB1*1401-DQA1*0101-DQB1*0503, DRB1*1501-DQA1*0102-DQB1*0602, DRB1*1104-DQA1*0501-DQB1*0301, DRB1*1303-DQA1*0501-DQB1*0301, DRB1*1301-DQA1*0103-DQB1*0603 and DRB1*0403-DQA1*0301-DQB1*0302 were considered protective. The distribution of protective, high-risk and other haplotypes were compared in the (first two) affected siblings and unaffected parents in the Canarian and non-Canarian Spanish families (chi-squared).Results:Complete unambiguous haplotypes were obtained and compared in Canarian (72 siblings with type 1 diabetes and 70 non-diabetic parents) and non-Canarian subjects(162 siblings with type 1 diabetes and 139 non-diabetic parents).Conclusion:Based on this family-based study, the high incidence of childhood-onset type 1 diabetes in the Canarian population does not seem to be explained by higher-risk class II HLA haplotypes.