Genetics of type 1 diabetes in Asian and Caucasian populations.

Among candidate genes for type 1 diabetes, HLA, INS, CTLA4, PTPN22 and SUMO4 have been shown to be associated with the disease in Caucasian populations. To clarify the similarities and differences in the contribution of these genes to type 1 diabetes between Asian and Caucasian populations, association of these genes with type 1 diabetes was studied in a large number of samples in Japanese and Korean populations. Class II HLA was strongly associated with type 1 diabetes in both Asian and Caucasian populations, but haplotypes associated with type 1 diabetes were markedly different due to difference in the presence and absence of haplotypes in each population. INS was consistently associated with type 1 diabetes in both Japanese and Caucasian populations, but frequency of disease-associated haplotype was markedly high in Japanese general population. CTLA4 was associated with type 1 diabetes only in a subset of patients with type 1 diabetes complicated with AITD in Japanese. A variant (R620W) of PTPN22 was associated with type 1 diabetes and other autoimmune diseases in Caucasians, but the variant was absent in Asians. SUMO4 was associated with type 1 diabetes in Asians, but not in Caucasian, suggesting a genetic heterogeneity among diverse ethnic groups. Trans-racial study with a large number of samples in both Asian and Caucasian populations will contribute to genetic dissection of type 1 diabetes and identification of causative variants.