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 < 0.0001), suggesting that risk alleles of these markers are preferably inherited jointly. For the bearers of C-G-C haplotype (consisting of rs7975232, rs1544410, and rs731236 unfavorable alleles), the risk of PMO was significantly higher (OR = 4.7, 95% CI 2.8–8.1, p < 0.0001) compared to controls. This haplotype was significantly over-represented in PMO group compared to all other haplotypes. Our findings highlight the importance of identified haplotypes of VDR gene variants. Complex screening of these genetic markers can be used to implement personalized clinical approach for prevention, treatment, and rehabilitation programs.

Effect of Cdx2 Polymorphism on the Relationship between Dietary Calcium Intake and Peak Bone Mass in Young Japanese Women

“…The genotype frequency in this study was in accordance with those of the Hardy-Weinberg equilibrium and previous studies involving Japanese participants [13,17]. While many studies have not demonstrated a relationship between the Cdx2 polymorphism and bone mineral density [13,14,16,17,[28][29][30][31][32][33][34][35], some have identified relationships [36,37]. This inconsistency might be due to relatively small study sample sizes or a wide range of age.…”

Vitamin D receptor (VDR) gene FokI, BsmI, ApaI, and TaqI polymorphisms and osteoporosis risk: a meta-analysis

“…Yadav et al Egyptian Journal of Medical Human Genetics (2020) 21:15[24,28,30,38,44,45,48,51,56,63,64,66,69,71,73,75,77,79,81,[83][84][85][87][88][89][90][91][92][93][94][95].…”

Vitamin D Receptor Polymorphism and Myasthenia Gravis in Chinese Han Population

“…Previous studies found that rs7975232, rs731236, and rs1544410 variants were in strong linkage disequilibrium ( 30 ), and we also performed haplotype analysis. We found that rs9729, rs3847987, rs739837, rs731236, rs7975232, rs10875692, and rs757343 were in high linkage disequilibrium, but there were no significant differences in haplotype frequencies between MG and the control group, which suggested that these haplotypes were not significantly related to the susceptibility of MG.…”