Association of PTPN22 haplotypes with type 1 diabetes in the Japanese population

The R620W polymorphism in the protein-tyrosine-phosphatase nonreceptor type 22 gene (PTPN22) confers susceptibility to type 1 diabetes (T1D) and other autoimmune diseases. This polymorphism is reportedly nonpolymorphic in the Asian population. Additional polymorphisms and specific haplotypes have also been associated with T1D, rheumatoid arthritis (RA) and Graves' disease in Caucasians. We examined whether PTPN22 single nucleotide polymorphisms (SNPs) other than R620W and haplotypes are associated with T1D in the Japanese population. We compared the allele frequencies of five haplotype-tagging SNPs in the PTPN22 gene, 2 of which are reportedly associated with RA in Caucasians (rs3789604 and rs1310182), and compared haplotype distributions between 184 Japanese T1D patients and 179 healthy controls. rs3789604 was not associated with T1D in our Japanese subjects. The frequency of the C allele of rs1310182 differed significantly between T1D patients and controls. Permutation analysis revealed the distribution of this haplotype to differ significantly between T1D patients and controls. One rare haplotype that included the susceptibility allele of rs1310182 was more frequent, while another rare haplotype that included the protective allele of rs1310182 was absent, in T1D patients. This significant haplotype distribution difference suggests that polymorphisms in the PTPN22 gene other than R620W are involved in either predisposition to or protection from T1D in the Japanese population.