rs2841277 (PLD4) is associated with susceptibility and rs4672495 is associated with disease activity in rheumatoid arthritis

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, can lead to long-term joint damage, chronic pain, and loss of motor function in the hands, and may share some common genetic factors with other autoimmune disorders, such as ankylosing spondylitis (AS). Many single-nucleotide polymorphisms (SNPs) were reported by genome-wide association studies (GWASs) of RA, but some of them have not been examined in the Taiwanese population. In this study, for 15 SNPs reported in previous RA and AS GWASs, we investigated their association with RA in a Taiwanese population. Based on 334 RA patients recruited from the Taichung Veterans General Hospital and 16,036 healthy subjects from the Taiwan Biobank (TWB) project, we observed that subjects having minor allele C at rs2841277 (phospholipase D family, member 4 (PLD4)) have lower susceptibility of RA, compare to those having genotype TT (Odds ratio (OR) = 0.6, p = 3.0 × 10-6). Among the RA patients, we observed that subjects having GG at rs4672495 have a lower proportion of severe RA, compare to other subjects (OR = 0.09, p = 5.6 × 10-3). Results of a bioinformatics approach showed that rs2841277 is able to influence expression of LINC00638 and AHNAK2 and rs4672495 is able to influence the expression of B3GNT2. In summary, this study replicated an association of rs2841277 with RA susceptibility and showed an AS-associated SNP, rs4672495, is associated with RA activity in the Taiwanese population.