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

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/d...

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Detalles Bibliográficos
Autores principales: Sugiura, Tomoko, Kawaguchi, Yasushi, Goto, Kanako, Hayashi, Yukiko, Gono, Takahisa, Furuya, Takefumi, Nishino, Ichizo, Yamanaka, Hisashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954551/
https://www.ncbi.nlm.nih.gov/pubmed/24632671
http://dx.doi.org/10.1371/journal.pone.0090019
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author Sugiura, Tomoko
Kawaguchi, Yasushi
Goto, Kanako
Hayashi, Yukiko
Gono, Takahisa
Furuya, Takefumi
Nishino, Ichizo
Yamanaka, Hisashi
author_facet Sugiura, Tomoko
Kawaguchi, Yasushi
Goto, Kanako
Hayashi, Yukiko
Gono, Takahisa
Furuya, Takefumi
Nishino, Ichizo
Yamanaka, Hisashi
author_sort Sugiura, Tomoko
collection PubMed
description 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.
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spelling pubmed-39545512014-03-18 Association between a C8orf13–BLK Polymorphism and Polymyositis/Dermatomyositis in the Japanese Population: An Additive Effect with STAT4 on Disease Susceptibility Sugiura, Tomoko Kawaguchi, Yasushi Goto, Kanako Hayashi, Yukiko Gono, Takahisa Furuya, Takefumi Nishino, Ichizo Yamanaka, Hisashi PLoS One Research Article 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. Public Library of Science 2014-03-14 /pmc/articles/PMC3954551/ /pubmed/24632671 http://dx.doi.org/10.1371/journal.pone.0090019 Text en © 2014 Sugiura et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sugiura, Tomoko
Kawaguchi, Yasushi
Goto, Kanako
Hayashi, Yukiko
Gono, Takahisa
Furuya, Takefumi
Nishino, Ichizo
Yamanaka, Hisashi
Association between a C8orf13–BLK Polymorphism and Polymyositis/Dermatomyositis in the Japanese Population: An Additive Effect with STAT4 on Disease Susceptibility
title Association between a C8orf13–BLK Polymorphism and Polymyositis/Dermatomyositis in the Japanese Population: An Additive Effect with STAT4 on Disease Susceptibility
title_full Association between a C8orf13–BLK Polymorphism and Polymyositis/Dermatomyositis in the Japanese Population: An Additive Effect with STAT4 on Disease Susceptibility
title_fullStr Association between a C8orf13–BLK Polymorphism and Polymyositis/Dermatomyositis in the Japanese Population: An Additive Effect with STAT4 on Disease Susceptibility
title_full_unstemmed Association between a C8orf13–BLK Polymorphism and Polymyositis/Dermatomyositis in the Japanese Population: An Additive Effect with STAT4 on Disease Susceptibility
title_short Association between a C8orf13–BLK Polymorphism and Polymyositis/Dermatomyositis in the Japanese Population: An Additive Effect with STAT4 on Disease Susceptibility
title_sort association between a c8orf13–blk polymorphism and polymyositis/dermatomyositis in the japanese population: an additive effect with stat4 on disease susceptibility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954551/
https://www.ncbi.nlm.nih.gov/pubmed/24632671
http://dx.doi.org/10.1371/journal.pone.0090019
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