Genetic variant association of PTPN22, CTLA4, IL2RA, as well as HLA frequencies in susceptibility to alopecia areata

Alopecia areata (AA) is characterized by a genetically complex inheritance. HLA frequencies, as well as the single nucleotide polymorphism (SNP) in PTPN22, CTLA4, and IL2RA genes, have been described to be associated with AA susceptibility. So far, no independent replication of these studies has been reported, and no data exist on a possible association between AA disease and these SNPs or influence of HLA frequencies in Iranian population. A possible association between HLA-DRB1*11 alleles as well as a single variation in PTPN22, CTLA4, and IL2RA genes and patchy AA disease have been investigated in a cohort from Iran. Patient and control subjects were genotyped for PTPN22 (rs2476601), CTLA4 (rs3087243), and IL2RA (rs3118470) variations as well as HLA frequencies. Gene expression levels were analyzed by real-time RT-PCR. In contrast to PTPN22 and CTLA4 gene polymorphisms, a significant association was found between IL2RA SNP and susceptibility to AA in Iranian cohort. While gene expression levels of IL2RA and PTPN22 were higher in the patients than that of controls, CTLA4 expression levels found significantly lower in the patients. Despite a significant association between AA and HLA-DRB1*11 frequencies, the presence of DRB1*11 is not associated with PTPN22, CTLA4, or IL2RA gene SNPs. Although the minor allele in IL2RA SNP can be a significant determinant of AA disease development in Iranian population, reported an association between the PTPN22 and CTLA4 variations was not confirmed by our study. Furthermore, these genetic risk factors might act independently from HLA alleles.