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The influence of vitamin D receptor genetic variants on bone mineral density and osteoporosis in Chinese postmenopausal women.

ABSTRACT: Growing evidence indicates that the vitamin D receptor (VDR) gene is an important candidate gene for influencing the development of osteoporosis. The aim of the study was to evaluate the potential association between genetic variants of VDR gene and bone mineral density (BMD) and osteoporosis in Chinese postmenopausal women. The study included 970 Chinese postmenopausal women at the postmenopausal osteoporosis (482) and healthy controls (488). The BMD of lumbar spine (L(2-4) anterior-posterior view), femoral neck hip, and total hip was evaluated using the Norland XR-46 dual energy X-ray absorptiometry (DEXA). The genotypes of VDR genetic variants were determined by the created restriction site-PCR (CRS-PCR) and confirmed by DNA sequencing methods. Our data indicated that the VDR p.Glicine (Gly)14 alanine (Ala) and p.histidine (His) 305 glutanine (Gln) genetic variants were statistically associated with adjusted femoral neck hip BMD, adjusted lumbar spine BMD, and adjusted total hip BMD (P values < 0.05). Results from this study suggest that the VDR p.Gly14Ala and p.His305Gln genetic variants are significantly associated with BMD decrease in Chinese postmenopausal women and might be used as molecular markers for assessing the risk of BMD and osteoporosis.

SUBMITTER: He W

PROVIDER: S-EPMC4346683 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The influence of vitamin D receptor genetic variants on bone mineral density and osteoporosis in Chinese postmenopausal women.

He Wei W Liu Ming M Huang Xiaonan X Qing Zuhong Z Gao Wei W

Disease markers 20150217

Growing evidence indicates that the vitamin D receptor (VDR) gene is an important candidate gene for influencing the development of osteoporosis. The aim of the study was to evaluate the potential association between genetic variants of VDR gene and bone mineral density (BMD) and osteoporosis in Chinese postmenopausal women. The study included 970 Chinese postmenopausal women at the postmenopausal osteoporosis (482) and healthy controls (488). The BMD of lumbar spine (L(2-4) anterior-posterior v ...[more]

PMID: 25784778

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Project description:BACKGROUND:The study investigated the associations of rs9340799:A?>?G (XbaI) and rs2234693:T?>?C (PvuII) polymorphisms in the estrogen receptor 1 gene (ESR1) with femoral neck (BMD-FN) and lumbar spine bone mineral density (BMD-LS), biochemical markers of bone turnover, calcium and phosphate levels, fracture prevalence, and a response to two types of anti-osteoporotic therapy in postmenopausal women from southern Slovakia. METHODS:We analysed 343 postmenopausal Slovak women (62.40?±?0.46 years). The influence of rs9340799 (AA vs. AG?+?GG) and rs2234693 (TT vs. TC?+?CC) genotypes on BMD and biochemical markers was evaluated by covariance analysis adjusted for age and BMI. Binary logistic regression was used to evaluate the genotype effect on fracture prevalence. Pharmacogenetic part of the study included women who received a regular therapy of HT (17ß estradiol with progesterone; 1 mg/day for both; N?=?76) or SERMs/raloxifene (60 mg/day; N?=?64) during 48 months. The genotype-based BMD change was assessed by variance analysis for repeated measurements. RESULTS:Women with AA genotype of rs9340799 had higher BMD-FN (+?0.12?±?0.57 of T-score) and BMD-LS (+?0.17?±?0.08 of T-score) in comparison with AG?+?GG. The rs2234693 polymorphism did not affect any of the monitored parameters. No effect of any ESR1 polymorphisms was found on fracture prevalence. Both types of anti-osteoporotic therapy had a positive effect on BMD improvement in FN and LS sites. Considering the effect of the ESR1 gene within the HT, the subjects with rs9340799/AA genotype showed worse response than those with GG genotype (-?0.26?±?0.10 of BMD-FN T-score; -?0.35?±?0.10 of BMD-LS T-score) and also with AG genotype (-?0.22?±?0.08 of BMD-LS T-score). The rs2234693/TT genotype responded poorer in BMD-LS in comparison with TC (-?0.22?±?0.08 of T-score) and CC (-?0.35?±?0.09 of T-score). The effect of the ESR1 gene on raloxifene therapy was reported only in BMD-LS. Subjects with rs9340799/AA genotype had a?-?0.30?±?0.11 of T-score worse response compared to AG genotype. The rs2234693/TT genotype showed -?0.39?±?0.11 and?-?0.46?±?0.15 lower T-scores in comparison with TC and CC genotypes, respectively. CONCLUSIONS:The rs9340799 polymorphism may contribute to decreased BMD in postmenopausal women from southern Slovakia; however, this is not related to higher fracture prevalence. Concurrently, both polymorphisms affected a response to analysed anti-osteoporotic therapies.

Project description:Abaloparatide increased ultradistal radius bone mineral density (BMD) in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Over the subsequent 24 months in ACTIVExtend, ultradistal radius BMD gains were maintained with alendronate. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE.IntroductionAbaloparatide (ABL) increased femoral neck, total hip, and lumbar spine bone mineral density (BMD) in postmenopausal women with osteoporosis and decreased the risk of vertebral and nonvertebral fractures in ACTIVE. Effects on fracture risk and BMD were maintained subsequently with alendronate (ALN) in ACTIVExtend. In a prespecified subanalysis of ACTIVE, ABL also increased BMD at the ultradistal radius. Our objective was to determine the efficacy of ABL followed by ALN vs placebo (PBO) followed by ALN on forearm BMD and fracture risk over 43 months in ACTIVExtend.MethodsUltradistal and 1/3 radius BMD (ACTIVE baseline to month 43) were measured (ABL/ALN, n?=?213; PBO/ALN, n?=?233). Wrist fracture rates were estimated for the ACTIVExtend intent-to-treat population (ABL/ALN, n?=?558; PBO/ALN, n?=?581) by Kaplan-Meier (KM) method.ResultsAt cumulative month 25, mean increase from ACTIVE baseline in ultradistal radius BMD was 1.1% (standard error, 0.49%) with ABL/ALN vs -?0.8% (0.43%) with PBO/ALN (P?<?0.01). BMD increases with ABL were maintained with ALN through month 43 in ACTIVExtend. BMD decreases at the 1/3 radius in ACTIVE (similar with ABL and PBO) were maintained through 24 months of ALN treatment in ACTIVExtend. Wrist fractures over 43 months occurred in 15 women with ABL/ALN (KM estimate, 2.8%) and 20 with PBO/ALN (KM estimate, 3.6%) (HR?=?0.77, 95% CI 0.39, 1.50; P?=?not significant).ConclusionUltradistal radius BMD gains following treatment with ABL in ACTIVE were maintained over 24 months of ALN treatment in ACTIVExtend. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE.Trial registrationClinicalTrials.gov : NCT01657162 submitted July 31, 2012.

Dataset Information

The influence of vitamin D receptor genetic variants on bone mineral density and osteoporosis in Chinese postmenopausal women.

Publications

The influence of vitamin D receptor genetic variants on bone mineral density and osteoporosis in Chinese postmenopausal women.

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