title: 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.
abstract: BACKGROUND
  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.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikari
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Furuya
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Taniguchi
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Momohara
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications*; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006620:Hip Fractures / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012306:Risk
chemical_list: D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human
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