Allele and haplotype frequency distribution in PTPN22 gene across variable ethnic groups: Implications for genetic association studies for autoimmune diseases.

The rs2476601-T allele at the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene has been consistently associated with several autoimmune diseases in European-derived populations. However, little is known about the allele and haplotype frequency distributions in PTPN22 among populations derived from other ethnic groups. In the present study, the allele and haplotype frequency distributions of six single nucleotide polymorphisms (SNPs) in the PTPN22 gene were compared among Brazilian populations and HapMap phase 3 dataset. A total of 10 different population samples were evaluated. Additionally, in admixed populations, individual genetic ancestries were estimated for Native American, African, and European contributions. Estimated individual ancestries were used as quantitative traits in a conditional approach for single-marker and haplotype-specific regression analyses. It was shown that several SNPs and haplotypes have different frequencies among different ethnic populations. Individual genetic ancestries were not associated with the rs2476601-T allele, but were associated with PTPN22 haplotypes in Brazilian, Mexican, and African-American admixed populations. Our results suggest caution in the interpretation of results found in association studies involving PTPN22 polymorphisms in admixed populations. Correction for stratification generated by admixture should be mandatory to minimize or avoid chances of spurious association.