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. 2014 Mar 20;16(2):R75.
doi: 10.1186/ar4516.

A GC polymorphism associated with serum 25-hydroxyvitamin D level is a risk factor for hip fracture in Japanese patients with rheumatoid arthritis: 10-year follow-up of the Institute of Rheumatology, Rheumatoid Arthritis cohort study

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

A GC polymorphism associated with serum 25-hydroxyvitamin D level is a risk factor for hip fracture in Japanese patients with rheumatoid arthritis: 10-year follow-up of the Institute of Rheumatology, Rheumatoid Arthritis cohort study

Shinji Yoshida et al. Arthritis Res Ther. .

Abstract

Introduction: Vitamin D deficiency has been reported to be common in patients with rheumatoid arthritis (RA) who have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Genetic variants affecting serum 25-hydroxyvitamin D (25(OH)D) concentration, an indicator of vitamin D status, were recently identified by genome-wide association studies of Caucasian populations. The purpose of this study was to validate the association and to test whether the serum 25(OH)D-linked genetic variants were associated with the occurrence of hip fracture in Japanese RA patients.

Methods: DNA samples of 1,957 Japanese RA patients were obtained from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort DNA collection. First, five single nucleotide polymorphisms (SNPs) that were reported to be associated with serum 25(OH)D concentration by genome-wide association studies were genotyped. The SNPs that showed a significant association with serum 25(OH)D level in the cross-sectional study were used in the longitudinal analysis of hip fracture risk. The genetic risk for hip fracture was determined by a multivariate Cox proportional hazards model in 1,957 patients with a maximum follow-up of 10 years (median, 8 years).

Results: Multivariate linear regression analyses showed that rs2282679 in GC (the gene encoding group-specific component (vitamin D binding protein)) locus was significantly associated with lower serum 25(OH)D concentration (P = 8.1 × 10⁻⁵). A Cox proportional hazards model indicated that rs2282679 in GC was significantly associated with the occurrence of hip fracture in a recessive model (hazard ratio (95% confidence interval) = 2.52 (1.05-6.05), P = 0.039).

Conclusions: A two-staged analysis demonstrated that rs2282679 in GC was associated with serum 25(OH)D concentration and could be a risk factor for hip fracture in Japanese RA patients.

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Figures

Figure 1
Figure 1
Boxplots representing the distribution of serum 25(OH)D concentration according to the number of the risk allele of rs2282679 (minor allele, C) in the GC locus. Each box represents the IQR range of values, with the bold line showing the median value. The vertical lines show maximum and minimum values that fall within 1.5 box lengths, the open circles show extreme values >1.5 box plot lengths.
Figure 2
Figure 2
Cumulative incidence of hip fracture for patients who were homozygous or heterozygous for the non-risk allele and patients homozygous for the risk allele of each single nucleotide polymorphism (analyzed by the Kaplan-Meier method). Homozygous for the risk allele of rs2282679 (C) in the GC locus, a serum 25(OH)D-linked genetic variant, was significantly associated with the occurrence of hip fracture.
See this image and copyright information in PMC

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