Abstract
IntroductionVitamin 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.MethodsDNA 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).ResultsMultivariate 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).ConclusionsA 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.
Highlights
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
Significant associations of vitamin D deficiency were found with some independent clinical risk factors: female gender, younger age, high disability score in the Japanese version of the Health Assessment Questionnaire (J-HAQ), low serum total protein level, low serum total cholesterol level, high serum alkaline phosphate (ALP) level, and use of non-steroidal antiinflammatory drugs (NSAIDs) [12]
We have previously shown that a high J-HAQ disability score, advanced age, history of total knee replacement (TKR), and low body mass index (BMI) were clinical risk factors for the occurrence of hip fracture in Japanese patients with RA [16]
Summary
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. 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. Vitamin D plays an important role in the maintenance of the musculoskeletal system. It is positively associated with muscle strength and physical performance, and is negatively associated with fall and fracture risk [8,9,10,11]. Significant associations of vitamin D deficiency were found with some independent clinical risk factors: female gender, younger age, high disability score in the Japanese version of the Health Assessment Questionnaire (J-HAQ), low serum total protein level, low serum total cholesterol level, high serum alkaline phosphate (ALP) level, and use of non-steroidal antiinflammatory drugs (NSAIDs) [12]
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