Association between a C8orf13–BLK Polymorphism and Polymyositis/Dermatomyositis in the Japanese Population: An Additive Effect with STAT4 on Disease

Background: Accumulating evidence has shown that several non-HLA genes are involved in the susceptibility to polymyositis/dermatomyositis. This study aimed to investigate the involvement of C8orf13–BLK, one of the strongest candidate genes for autoimmune diseases, in susceptibility to polymyositis/dermatomyositis in the Japanese population. A possible gene–gene interaction between C8orf13–BLK and STAT4, which we recently showed to be associated with Japanese polymyositis/dermatomyositis, was also analyzed. Methods: A single-nucleotide polymorphism in C8orf13–BLK (dbSNP ID: rs13277113) was investigated in the Japanese population using a TaqMan assay in 283 polymyositis patients, 194 dermatomyositis patients, and 656 control subjects. Results: The C8orf13–BLK rs13277113A allele was associated with overall polymyositis/dermatomyositis (P,0.001, odds ratio [OR] 1.44, 95 % confidence interval [CI] 1.19–1.73), as well as polymyositis (P = 0.011, OR 1.32, 95 % CI 1.06–1.64) and dermatomyositis (P,0.001, OR 1.64, 95 % CI 1.26–2.12). No association was observed between the C8orf13–BLK rs13277113A allele and either interstitial lung disease or anti-Jo-1 antibody positivity. The C8orf13–BLK rs13277113 A and STAT4 rs7574865 T alleles had an additive effect on polymyositis/dermatomyositis susceptibility. The strongest association was observed in dermatomyositis, with an OR of 3.07 (95 % CI; 1.57–6.02) for the carriers of four risk alleles at the two SNP sites, namely, rs1327713 and rs7574865