Abstract:

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.
CONCLUSIONS: This study established C8orf13-BLK as a new genetic susceptibility factor for polymyositis/dermatomyositis. Both C8orf13-BLK and STAT4 exert additive effects on disease susceptibility. These observations suggested that C8orf13-BLK, in combination with STAT4, plays a pivotal role in creating genetic susceptibility to polymyositis/dermatomyositis in Japanese individuals.

日本語要旨:

以前の研究で、C13orf-BLK遺伝子上に存在するSNP (rs13277113) は、いくつかの自己免疫疾患患者において優位に認められた。今回の研究ではrs13277113が日本人皮膚筋炎、多発筋炎患者にも優位に認められ、疾患感受性を上昇させることを示唆された。さらに,以前に皮膚筋炎、多発筋炎発症との相関が認められたSTAT4遺伝子上のSNP (rs7574865) とSNP (rs13277113) 相乗的な作用を持つことが示唆された。本研究によりC13orf-BLK、STAT4遺伝子の皮膚筋炎、多発筋炎発症における重要性が示唆された。