Abstract
IntroductionPatients 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.MethodsDNA 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.ResultsThe 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.ConclusionsOur results indicate that an OPG allele is associated with increased risk for hip fracture in Japanese patients with RA.
Highlights
Patients with rheumatoid arthritis (RA) have a higher prevalence of osteoporosis and hip fracture than healthy individuals
Rheumatoid arthritis (RA) is a complex polygenic disorder of unknown etiology characterized by chronic inflammation and joint destruction, resulting in deteriorated physical function and increased risk of falling. [1,2,3] Patients with RA have a higher prevalence of osteoporosis and hip fracture than healthy individuals. [4,5,6] Several clinical risk factors for osteoporotic fracture in RA patients have been reported far
[7] Bone mineral density (BMD) is the major predictor of osteoporotic fracture, [5] and the fracture risk assessment tool was developed based on the use of clinical risk factors, including the presence of RA
Summary
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. [1,2,3] Patients with RA have a higher prevalence of osteoporosis and hip fracture than healthy individuals. [8] Recently, multiple genetic risk loci for BMD and osteoporotic fracture were identified in a meta-analysis of genome-wide association studies in people of European descent. The purpose of the present study was to validate the association and to identify genetic variants associated with the occurrence of hip fracture in Japanese patients with RA. We hope that results from this study will increase our understanding of the genetic basis of hip fracture
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