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A meta-analysis of VDR polymorphisms and postmenopausal osteoporosis.

ABSTRACT: Background:Whether polymorphisms in VDR gene affect the risk of postmenopausal osteoporosis or not remain unclear. Thus, the authors performed a meta-analysis to more robustly assess associations between polymorphisms in VDR gene and the risk of postmenopausal osteoporosis by integrating the results of previous literature. Methods:Medline, Embase, Wanfang, VIP and CNKI were searched comprehensively for eligible literature, and 67 genetic association studies were finally selected to be included in this meta-analysis. Results:We found that ApaI rs7975232 (dominant comparison: OR = 0.77, P = 0.007; allele comparison: OR = 0.81, P = 0.04), BsmI rs1544410 (dominant comparison: OR = 0.69, P = 0.002; allele comparison: OR = 0.78, P = 0.008) and TaqI rs731236 (recessive comparison: OR = 1.32 , P = 0.01) polymorphisms were significantly associated with the risk of postmenopausal osteoporosis in Caucasians, whereas FokI rs10735810 polymorphism was significantly associated with the risk of postmenopausal osteoporosis in Asians (dominant comparison: OR = 0.61, P = 0.0001; recessive comparison: OR = 2.02, P = 0.001; allele comparison: OR = 0.68, P = 0.002). Conclusions:This meta-analysis shows that ApaI rs7975232, BsmI rs1544410 and TaqI rs731236 polymorphisms may affect the risk of postmenopausal osteoporosis in Caucasians, while BsmI rs1544410 polymorphism may affect the risk of postmenopausal osteoporosis in Asians.

SUBMITTER: Fu L

PROVIDER: S-EPMC7583137 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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A meta-analysis of VDR polymorphisms and postmenopausal osteoporosis.

Fu Lijuan L Ma Jinhuan J Yan Sumei S Si Qijun Q

Endocrine connections 20201001 9

<h4>Background</h4>Whether polymorphisms in VDR gene affect the risk of postmenopausal osteoporosis or not remain unclear. Thus, the authors performed a meta-analysis to more robustly assess associations between polymorphisms in VDR gene and the risk of postmenopausal osteoporosis by integrating the results of previous literature.<h4>Methods</h4>Medline, Embase, Wanfang, VIP and CNKI were searched comprehensively for eligible literature, and 67 genetic association studies were finally selected t ...[more]

PMID: 32738125

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Project description:The correlation of genetic polymorphisms of GALNT3 and vitamin D receptor (VDR) with osteoporosis in postmenopausal women was investigated. A total of 1,212 cases of postmenopausal patients diagnosed with osteoporosis (observation group) and 404 cases of postmenopausal women without osteoporosis (control group) were selected. Dual-energy X-ray absorptiometry was used for measurement of bone mineral density (BMD) of lumbar vertebrae L2-4, proximal femoral neck and total hip, and classifications were made. TaqMan genotyping technology was employed to examine tag single-nucleotide polymorphism (tagSNP) of GALNT3 and VDR and the correlation of tagSNP with bone turnover markers (BTMs) and serum calcium and phosphorous levels was analyzed. The multiple logistic regression analysis was used to screen risk factors for osteoporosis. A comparison of age and menopause time of the two groups, yielded no statistical significance difference (P>0.05). BMD and T values of the lumbar vertebrae, femoral neck and total hip in the observation group were significantly lower than those in the control group, and the differences were statistically significant (P<0.05). A comparison of the degree of osteoporosis, yielded statistically significant differences (P<0.05). The proportion of tagSNP of 5 loci in GALNT3 and 3 loci in VDR in the observation group was significantly higher than that in the control group, and the differences were of statistical significance (P<0.05). Levels of 25-OHD3, ?-CTX, P1NP and serum calcium in the observation group were lower than those in the control group and the level of serum phosphorus in the observation group was higher than that in the control group, and all of these results were statistically significant (P<0.05). The result of the correlation analysis revealed that rs1425000 and rs757343 were negatively correlated with BTM and serum calcium and phosphorus levels (P<0.05). The result of the regression analysis revealed that 8 tagSNPs were independent risk factors for osteoporosis. Genetic polymorphisms of GALNT3 and VDR were closely associated with osteoporosis in postmenopausal women.

Project description:Determining molecular markers for osteoporosis may be valuable for improving the quality of life of affected elderly patients by aiding in early detection and disease management. In the present study, the association between single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) and tumour necrosis factor superfamily number 11 (TNFSF11) genes and the susceptibility of developing osteoporosis was investigated in a Thai female cohort. The study group consisted of 105 Thai postmenopausal patients diagnosed with osteoporosis and 132 healthy Thai postmenopausal female volunteers. DNA extracted from blood samples was used to genotype the VDR and TNFSF11 genes using polymerase chain reaction-restriction fragment length polymorphism and sequencing analysis. For VDR, the frequencies of the genotypes TT, CT and CC for the TaqI SNP (rs731236) were 87.88, 11.36 and 0.76%, respectively, in the control group, while in the osteoporosis cohort were 92.38, 5.71 and 1.91%, respectively. For the FokI SNP (rs2228570), the frequencies of the genotypes CC, CT and TT were 31.06, 55.30 and 13.64%, respectively, in the control group, and in the osteoporosis group were 29.52, 43.81 and 26.67%, respectively. For BsmI SNP (rs1544410), the frequencies of the genotypes GG, GA and AA were 78.03, 18.94 and 3.03%, respectively, in control group, and in the osteoporosis group were 80.95, 18.10 and 0.95%, respectively. The significant risk of osteoporosis associated with the FokI SNP was determined. The odds ratio (95% confidence interval) was 2.30 (1.14-4.69; P=0.01) among patients with osteoporosis with TT as the susceptibility genotype. For TNFSF11, the frequencies of the genotypes TT, CT and CC for the -290C>T SNP (rs9525641) in the control group were 36.36, 50.76 and 12.88%, respectively, while in the osteoporosis group were 31.43, 56.19 and 12.38%, respectively. For the -643C>T SNP (rs9533156), the frequencies of the genotypes TT, CT and CC in the control group were 35.61, 48.48 and 15.91%, respectively, while in the osteoporosis group were 32.38, 55.24 and 12.38%, respectively. For the -693G>C SNP (rs9533155), the frequencies of the genotypes CC, CG, and GG in the control group were 39.39, 46.97 and 13.64%, respectively, and in the osteoporosis group were 36.19, 53.33 and 10.48%, respectively. No significant associations of the TNFSF11 SNPs with osteoporosis were determined; however, it was notable that the GCT haplotype of TNFSF11 may be a protective haplotype for osteoporosis. Therefore, it was concluded that the SNP FokI of VDR may be a potential molecular biomarker for the development of osteoporosis in Thai females.

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A meta-analysis of VDR polymorphisms and postmenopausal osteoporosis.

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A meta-analysis of VDR polymorphisms and postmenopausal osteoporosis.

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