Dataset Information

Association of Vitamin D Receptor Gene Variation With Osteoporosis Risk in Belarusian and Lithuanian Postmenopausal Women.

ABSTRACT: Vitamin D receptor (VDR) is one of the main mediators of vitamin D biological activity. VDR dysfunction might substantially contribute to development of postmenopausal osteoporosis (PMO). Numerous studies have revealed the effects of several VDR gene variants on osteoporosis risk, although significant variation in different ethnicities have been suggested. The main purpose of this work was to assess the frequency of distribution of VDR genetic variants with established effect and evaluate their haplotype association with the risk of PMO in a cohort of Belarusian and Lithuanian women. Case group included women with PMO (n?=?149), the control group comprised women with normal bone mineral density (BMD) and without previous fragility fractures (n?=?172). Both groups were matched for age, height, sex, and BMI-no statistically significant differences observed. VDR gene polymorphic variants (ApaI rs7975232, BsmI rs1544410, TaqI rs731236, and Cdx2 rs11568820) were determined using polymerase chain reaction and restriction fragment length polymorphism. The lumbar spine (L1-L4) and femoral neck BMD was measured using dual-energy X-ray absorptiometry. Association between each VDR variant and PMO risk was assessed using multiple logistic regression. The genotyping revealed statistically significant difference in the rs7975232 genotype frequencies between the patients and the controls (homozygous C/C genotype was overrepresented in patients, p?=?0.008). Patients with osteoporosis were also three times more likely to carry the rs1544410 G/G genotype, when compared to controls. We found that rs7975232, rs1544410, and rs731236 variants were in a strong direct linkage disequilibrium (p?

SUBMITTER: Marozik PM

PROVIDER: S-EPMC5996071 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Association of Vitamin D Receptor Gene Variation With Osteoporosis Risk in Belarusian and Lithuanian Postmenopausal Women.

Marozik Pavel M PM Tamulaitiene Marija M Rudenka Ema E Alekna Vidmantas V Mosse Irma I Rudenka Alena A Samokhovec Volha V Kobets Katsiaryna K

Frontiers in endocrinology 20180605

Vitamin D receptor (VDR) is one of the main mediators of vitamin D biological activity. VDR dysfunction might substantially contribute to development of postmenopausal osteoporosis (PMO). Numerous studies have revealed the effects of several <i>VDR</i> gene variants on osteoporosis risk, although significant variation in different ethnicities have been suggested. The main purpose of this work was to assess the frequency of distribution of <i>VDR</i> genetic variants with established effect and e ...[more]

PMID: 29922235

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Project description:Osteoporosis is a polygenic disorder and has been demonstrated to be associated with ~30 candidate genes, the majority of which have also been implicated in the regulation of bone mineral density (BMD). Vitamin D receptor (VDR) is the candidate gene that has been most extensively studied. Certain studies have reported that the VDR single nucleotide polymorphism ApaI is associated with the risk of osteoporosis in Caucasian and African women. However, this association has not yet been studied in postmenopausal Han Chinese women in the Xinjiang area. In the present study, ApaI polymorphisms of VDR were defined by polymerase chain reaction-restriction fragment length polymorphism, in order to analyze the distribution of ApaI polymorphisms in postmenopausal Han Chinese women from Xinjiang. BMD was measured by dual energy X-ray absorptiometry at the lumbar spine (L2-4), Ward's triangle, great trochanter and femoral shaft. A total of 336 women were included in this study. The genotype distribution of ApaI was consistent with the Hardy-Weinberg equilibrium (all P>0.05). There were no significant differences in ApaI genotype frequencies between the 90 cases in the osteoporosis group and 246 cases in the non-osteoporosis group (P=0.946). Meanwhile, it was identified that BMD values of the tested locations were negatively correlated with age (P<0.05) and positively correlated with body mass index (BMI; P<0.05). On further attribution risk analysis, BMD was identified as a risk factor [odds ratio (OR): 0.464, 95% confidence interval (CI): 0.372-0.580, P=0.001] and BMI a protective factor (OR: 1.502, 95% CI: 1.008-2.240, P=0.032) in osteoporosis. When BMD was adjusted for confounding factors including age and BMI, it was observed that the ApaI polymorphism was not associated with BMD at the sites tested (P>0.05). In conclusion, the present study identified no significant association of the common VDR polymorphism ApaI with BMD at several skeletal sites in postmenopausal Han Chinese women in the Xinjiang area. Age was negatively correlated with BMD at different sites and identified as a risk factor; while BMI was positively correlated with BMD and identified as a protective factor.

Project description:In elderly women with osteoporosis, prior fracture, low BMD, impaired physical functioning, poorer general health, and recent falls were all direct predictors of imminent (in next year) fracture risk. Prior fracture, older age, worse health, impaired cognitive functioning, and recent falls indirectly increased imminent risk by reducing physical functioning/general health. INTRODUCTION:This study was designed to examine determinants of imminent risk of osteoporotic fracture (i.e., next 1-2 years) in postmenopausal women. METHODS:This retrospective cohort study used data from Caucasian women age 65 or older with osteoporosis who participated in the observational Study of Osteoporotic Fractures (SOF). We examined potential direct and indirect predictors of hip and nonvertebral fractures in 1-year follow-up intervals including anthropometric measures, bone mineral density (T-score), fracture since age 50, physical function, cognition, medical conditions, recent (past year) falls, and lifestyle factors. Clinically related variables were grouped into constructs via factor analysis. These constructs and selected individual variables were incorporated into a theoretical structural equation model to evaluate factors that influence imminent risk. RESULTS:Among 2261 patients, 19.4% had a nonvertebral fracture and 5.5% had a hip fracture within 1 year of a study visit between 1992 and 2008. Prior fracture, lower T-scores, lower physical functioning, and recent falls all directly increased 1-year risk of nonvertebral fracture. For both nonvertebral and hip fractures, prior fracture and recent falls influenced risk indirectly through general health, while cognition influenced risk via physical functioning. Age influenced both physical functioning and general health. CONCLUSIONS:Several established risk factors for 10-year fracture risk also played a role in predicting imminent risk of fracture (e.g., T-scores, prior fracture), as did falls, cognition, physical functioning, and general health. Fracture risk assessments should also consider falls and fall risk factors as well as established bone-related risk factors in assessing imminent fracture risk.

Project description:INTRODUCTION:Long-term treatment is used in patients with osteoporosis, and bisphosphonates (BPs) are the most commonly prescribed medications. However, in some patients this therapy is not effective, cause different side effects and complications. Unfortunately, at least one year is needed to identify and confirm an ineffectiveness of BPs therapy on bone mineral density (BMD). Among other factors, a response to BPs therapy may also be explained by genetic factors. The aim of this study was to analyze the influence of SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 gene variants on the response to treatment with aminobisphosphonates. MATERIALS AND METHODS:Women with postmenopausal osteoporosis were included to this study if they used aminobisphosphonates for at least 12 months. Exclusion criteria were: persistence on BPs therapy less than 80%, bone metabolic diseases, diseases deemed to affect bone metabolism, malignant tumours, using of any medications influencing BMD. The study protocol was approved by the local ethics committee. The BMD at the lumbar spine and femoral neck were measured using dual x-ray absorptiometry (GE Lunar) before and at least 12 months after treatment with BPs. According to BMD change, patients were divided in two groups-responders and non-responders to BPs terapy. Polymorphic variants in SOST, PTH, FGF2, FDPS, GGPS1, and LRP5 genes were determined using PCR analysis with TaqMan probes (Thermo Scientific). RESULTS:In total, 201 women with BPs therapy were included in the study. No statistically significant differences were observed in age, age at menopause, weight, height, BMI and baseline BMD levels between responders (122 subjects) and non-responders (79 subjects). As single markers, the SOST rs1234612 T/T (OR = 2.3; P = 0.02), PTH rs7125774 T/T (OR = 2.8, P = 0.0009), FDPS rs2297480 G/G (OR = 29.3, P = 2.2×10-7), and GGPS1 rs10925503 C/C+C/T (OR = 2.9; P = 0.003) gene variants were over-represented in non-responders group. No significant association between FGF2 rs6854081 and LRP5 rs3736228 gene variants and response to BPs treatment was observed. The carriers of T-T-G-C allelic combination (constructed from rs1234612, rs7125774, rs2297480, and rs10925503) were predisposed to negative response to BPs treatment (OR = 4.9, 95% CI 1.7-14.6, P = 0.005). The C-C-T-C combination was significantly over-represented in responders (OR = 0.1, 95% CI 0.1-0.5, P = 0.006). CONCLUSIONS:Our findings highlight the importance of identified single gene variants and their allelic combinations for pharmacogenetics of BPs therapy of osteoporosis. Complex screening of these genetic markers could be used as a new strategy for personalized antiresorptive therapy.

Dataset Information

Association of Vitamin D Receptor Gene Variation With Osteoporosis Risk in Belarusian and Lithuanian Postmenopausal Women.

Publications

Association of Vitamin D Receptor Gene Variation With Osteoporosis Risk in Belarusian and Lithuanian Postmenopausal Women.

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