Association between a C8orf13-BLK polymorphism and polymyositis/dermatomyositis in the Japanese population: an additive effect with STAT4 on disease susceptibility.

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.

• Authors: Tomoko Sugiura, Yasushi Kawaguchi, Kanako Goto, Yukiko Hayashi, Takahisa Gono, Takefumi Furuya, Ichizo Nishino, Hisashi Yamanaka
• Journal: PloS one (PLoS One) Vol. 9 Issue 3 Pg. e90019 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24632671 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FAM167A protein, human
• Proteins
• STAT4 Transcription Factor

Topics

• Adult
• Asian People (genetics)
• Dermatomyositis (genetics)
• Female
• Genetic Predisposition to Disease (genetics)
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide (genetics)
• Polymyositis (genetics)
• Proteins (genetics, metabolism)
• STAT4 Transcription Factor (genetics, metabolism)