Genetics of rheumatoid arthritis: Underlying evidence of ethnic differences

A new age has begun in the genetics of rheumatoid arthritis (RA), as genome-wide association studies scanning the human genome have been put into practical use. Among the RA-susceptibility genes identified by genetic studies, HLA-DRB1 gene appears to represent the most major determinant of genetic predisposition to RA. However, inconsistent results of the contributions of non-HLA susceptibility genes have been described, with the exception of a few genes repeatedly associated with RA-susceptibility, such as PTPN22 gene in populations of European ancestry and PADI4 gene in populations of Asian ancestry, revealing the presence of genetic heterogeneity in RA. We review herein recent advances in the genetics of RA and discuss the underlying differences among populations of European and Asian ancestries, taking as examples our previous findings for RA-susceptibility genes in the Japanese population: PADI4; FCRL3; and CD244.