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

PLoS One. 2014 Aug 8;9(8):e104587. doi: 10.1371/journal.pone.0104587. eCollection 2014.

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / complications*
  • Asian People / genetics
  • Cohort Studies
  • Female
  • Genome-Wide Association Study
  • Hip Fractures / complications*
  • Hip Fractures / epidemiology
  • Hip Fractures / genetics*
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Osteoprotegerin / genetics*
  • Polymorphism, Single Nucleotide*
  • Proportional Hazards Models
  • Risk

Substances

  • Osteoprotegerin
  • TNFRSF11B protein, human

Grants and funding

This work was supported by grants provided by the Japanese Ministry of Education, Culture, Sports, Science and Technology Grant-in-Aid for Scientific Research (KI, SM), the Japanese Ministry of Health, Labour and Welfare (SM, HY). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.