An osteoprotegerin gene polymorphism is associated with an increased risk of hip fracture in Japanese patients with rheumatoid arthritis

Results from the IORRA observational cohort study

Shinji Yoshida, Katsunori Ikari, Takefumi Furuya, Yoshiaki Toyama, Atsuo Taniguchi, Hisashi Yamanaka, Shigeki Momohara

Research output: Contribution to journalArticle

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Abstract

Introduction: Patients with rheumatoid arthritis (RA) have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. The purpose of this study was to identify genetic variants associated with the occurrence of hip fracture in Japanese patients with RA. Methods: DNA samples from 2,282 Japanese patients with RA were obtained from the DNA collection of the Institute of Rheumatology Rheumatoid Arthritis cohort (IORRA) study. Six single nucleotide polymorphisms (SNPs) that have been reported to be associated with fractures in recent studies were selected and genotyped. Forty hip fractures were identified with a maximum follow-up of 10 years. The genetic risk for hip fracture was examined using a multivariate Cox proportional hazards regression model. Results: The risk analyses revealed that patients who are homozygous for the major allele of SNP rs6993813, in the OPG locus, have a higher risk for hip fracture (hazard ratio [95% CI] = 2.53 [1.29-4.95], P = 0.0067). No association was found for the other SNPs. Conclusions: Our results indicate that an OPG allele is associated with increased risk for hip fracture in Japanese patients with RA.

Original languageEnglish
Article numbere104587
JournalPLoS One
Volume9
Issue number8
DOIs
Publication statusPublished - 2014 Aug 8

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hip fractures
Osteoprotegerin
rheumatoid arthritis
Hip Fractures
Rheumatology
Polymorphism
cohort studies
Observational Studies
Rheumatoid Arthritis
Cohort Studies
Genes
genetic polymorphism
single nucleotide polymorphism
Single Nucleotide Polymorphism
genes
Nucleotides
Alleles
alleles
Hazards
loci

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

An osteoprotegerin gene polymorphism is associated with an increased risk of hip fracture in Japanese patients with rheumatoid arthritis : Results from the IORRA observational cohort study. / Yoshida, Shinji; Ikari, Katsunori; Furuya, Takefumi; Toyama, Yoshiaki; Taniguchi, Atsuo; Yamanaka, Hisashi; Momohara, Shigeki.

In: PLoS One, Vol. 9, No. 8, e104587, 08.08.2014.

Research output: Contribution to journalArticle

Yoshida, Shinji ; Ikari, Katsunori ; Furuya, Takefumi ; Toyama, Yoshiaki ; Taniguchi, Atsuo ; Yamanaka, Hisashi ; Momohara, Shigeki. / An osteoprotegerin gene polymorphism is associated with an increased risk of hip fracture in Japanese patients with rheumatoid arthritis : Results from the IORRA observational cohort study. In: PLoS One. 2014 ; Vol. 9, No. 8.
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abstract = "Introduction: Patients with rheumatoid arthritis (RA) have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. The purpose of this study was to identify genetic variants associated with the occurrence of hip fracture in Japanese patients with RA. Methods: DNA samples from 2,282 Japanese patients with RA were obtained from the DNA collection of the Institute of Rheumatology Rheumatoid Arthritis cohort (IORRA) study. Six single nucleotide polymorphisms (SNPs) that have been reported to be associated with fractures in recent studies were selected and genotyped. Forty hip fractures were identified with a maximum follow-up of 10 years. The genetic risk for hip fracture was examined using a multivariate Cox proportional hazards regression model. Results: The risk analyses revealed that patients who are homozygous for the major allele of SNP rs6993813, in the OPG locus, have a higher risk for hip fracture (hazard ratio [95{\%} CI] = 2.53 [1.29-4.95], P = 0.0067). No association was found for the other SNPs. Conclusions: Our results indicate that an OPG allele is associated with increased risk for hip fracture in Japanese patients with RA.",
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