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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 S, Ikari K, Furuya T, Toyama Y, Taniguchi A, Yamanaka H, Momohara S - PLoS ONE (2014)

Bottom Line: Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies.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.No association was found for the other SNPs.

View Article: PubMed Central - PubMed

Affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.

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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Related in: MedlinePlus

Cumulative incidence of hip fracture for patients who were homo- or heterozygous for the non-risk allele and patients homozygous for the risk allele of each single nucleotide polymorphism (by the Kaplan-Meier method).Homozygous for the risk allele of rs6993813 (C) in the OPG locus was significantly associated with the occurrence of hip fracture (P = 0.0067).
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pone-0104587-g001: Cumulative incidence of hip fracture for patients who were homo- or heterozygous for the non-risk allele and patients homozygous for the risk allele of each single nucleotide polymorphism (by the Kaplan-Meier method).Homozygous for the risk allele of rs6993813 (C) in the OPG locus was significantly associated with the occurrence of hip fracture (P = 0.0067).

Mentions: A multivariate Cox proportional hazards model revealed that patients who are homozygous for the major allele of SNP rs6993813, in the OPG locus, had a higher risk for hip fracture compared to other patients (HR [95% CI]  = 2.53 [1.29 to 4.95], P  = 0.0067 [α  = 0.0083 after Bonferroni correction], Table 2, Figure 1). No associations were found for the other SNPs (Table 2).


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 S, Ikari K, Furuya T, Toyama Y, Taniguchi A, Yamanaka H, Momohara S - PLoS ONE (2014)

Cumulative incidence of hip fracture for patients who were homo- or heterozygous for the non-risk allele and patients homozygous for the risk allele of each single nucleotide polymorphism (by the Kaplan-Meier method).Homozygous for the risk allele of rs6993813 (C) in the OPG locus was significantly associated with the occurrence of hip fracture (P = 0.0067).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126739&req=5

pone-0104587-g001: Cumulative incidence of hip fracture for patients who were homo- or heterozygous for the non-risk allele and patients homozygous for the risk allele of each single nucleotide polymorphism (by the Kaplan-Meier method).Homozygous for the risk allele of rs6993813 (C) in the OPG locus was significantly associated with the occurrence of hip fracture (P = 0.0067).
Mentions: A multivariate Cox proportional hazards model revealed that patients who are homozygous for the major allele of SNP rs6993813, in the OPG locus, had a higher risk for hip fracture compared to other patients (HR [95% CI]  = 2.53 [1.29 to 4.95], P  = 0.0067 [α  = 0.0083 after Bonferroni correction], Table 2, Figure 1). No associations were found for the other SNPs (Table 2).

Bottom Line: Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies.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.No association was found for the other SNPs.

View Article: PubMed Central - PubMed

Affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan; Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.

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.

Show MeSH
Related in: MedlinePlus