Vitamin D Receptor Gene Variants Susceptible to Osteoporosis in Arab Post-Menopausal Women

Post-menopausal osteoporosis (PMO) is a multifactorial bone disorder in elderly women. Various vitamin D receptor (VDR) gene variants have been studied and associated with osteoporosis in other populations, but not in a homogenous Arab ethnic group. Herein, the current study explores the association between VDR polymorphisms and susceptibility to osteoporosis in Saudi postmenopausal women. In total, 600 Saudi postmenopausal women (N = 300 osteoporosis; N = 300 control) were genotyped for VDR gene variants (rs7975232, rs1544410, rs731236) using TaqMan® SNP genotyping assays. Bone mineral density (BMD) for the lumbar spine and femur was assessed using dual-energy X-ray absorptiometry (DEXA). The heterozygous frequency distributions AC of rs7975232, CT of rs1544410, and AG of rs731236 were significantly higher in the osteoporosis group than controls (p < 0.05). Heterozygous AC of rs7975232 (1.6; 95% CI 1.1–2.3; p < 0.023), CT of rs1544410 (1.6; 95% CI 1.1–2.4; p < 0.022), and AG of rs731236 (1.6; 95% CI 1.1–2.4; p < 0.024) were significantly associated with increased risk of osteoporosis, independent of age and BMI. In conclusion, VDR gene variants rs7975232, rs1544410, rs731236 had a significant effect on BMD and were associated with osteoporosis risk in Saudi postmenopausal women.

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Are Vitamin D Deficiency and VDR Gene Polymorphisms Associated With Higher Blood Pressure Defined by the 2017 ACC/AHA in Postmenopausal Women?

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1483 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A729-A729

Author(s):

Betânia Rodrigues dos Santos ◽

Gislaine Casanova ◽

Thaís Rasia Silva ◽

Lucas Bandeira Marchesan ◽

Karen Oppermann ◽

...

Keyword(s):

Blood Pressure ◽

Vitamin D ◽

Vitamin D Deficiency ◽

Postmenopausal Women ◽

Gene Variants ◽

Vdr Gene ◽

Allelic Discrimination ◽

Increased Risk ◽

Vitamin D Levels ◽

Vdr Gene Polymorphisms

Abstract Postmenopausal status has been associated with an unfavorable phenotype tied to hormonal and metabolic changes, which collectively could contribute to an increased risk of cardiovascular disease. Vitamin D deficiency is frequent in postmenopausal women and may be linked to this phenotype and especially to an increased risk of developing hypertension. Vitamin D actions are modulated by the vitamin D receptor (VDR), and metabolic abnormalities have been associated with VDR gene variants in different populations. The aims of the present study were to assess the vitamin D levels, prevalence of vitamin D deficiency and genotypes of Fok-I, Bsm-I, Apa-I and Taq-I polymorphisms in the VDR gene and to determine whether vitamin D deficiency and VDR gene variants are associated with blood pressure levels and systemic arterial hypertension by the 2017 ACC/AHA definition in postmenopausal women. We conducted a cross-sectional study of biobanked blood samples from 339 postmenopausal women with no evidence of clinical disease. Blood pressure strata were defined according to the 2017 ACC/AHA cutoffs. Circulating 25(OH)D levels were considered deficient if <20 ng/mL. Genotype analysis was performed by RT-PCR with allelic discrimination assays. Mean serum total 25(OH)D levels were 22.99±8.54 ng/mL, and 40.1% of participants were deficient in vitamin D. Overall, 7.7% had elevated blood pressure, 36.6% had stage 1 and 37.8% had stage 2 hypertension. Mean total (p=0.014) and free 25(OH)D levels (p=0.029) were lower in women with stage 2 hypertension than in those with normal blood pressure. The CC+CT genotypes of Bsm-I and the AA+AG genotypes of Taq-I polymorphisms were more frequent in women with stage 2 hypertension (Bsm-I CC+CT: 85.8% vs. TT: 14.2%, p=0.045; Taq-I AA+AG: 91.3% vs. GG: 8.7%, p=0.021). A higher prevalence ratio of stage 2 hypertension was associated with age (PR 1.058; 95%CI 1.033-1.083; p<0.001), BMI (PR 1.046; 95%CI 1.025-1.068; p<0.001), vitamin D deficiency (PR 1.333; 95%CI 1.016-1.749; p=0.038) and Taq-I polymorphism (PR 1.764; 95%CI 1.030-3.019; p=0.039). Women with vitamin D deficiency and the AA+AG genotype of Taq-I polymorphism were 33% and 76% more likely to have stage 2 hypertension, respectively, but these analyses lost significance when adjusted for age and BMI. In conclusion, the present results suggest that vitamin D deficiency and Taq-I polymorphism are associated with stage 2 hypertension, depending on age and BMI, in postmenopausal women.

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Association of Polymorphisms of Interleukin-6, Osteocalcin, and Vitamin D Receptor Genes, Alone or in Combination, with Bone Mineral Density in Community-Dwelling Japanese Women and Men

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2002-021449 ◽

2003 ◽

Vol 88 (7) ◽

pp. 3372-3378 ◽

Cited By ~ 56

Author(s):

Yoshiji Yamada ◽

Fujiko Ando ◽

Naoakira Niino ◽

Hiroshi Shimokata

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Postmenopausal Women ◽

Bone Mineral ◽

Vitamin D Receptor ◽

Japanese Women ◽

Community Dwelling ◽

Mineral Density ◽

Vdr Gene ◽

Osteocalcin Gene

We examined whether the −634C→G, 298C→T, and 2C→T polymorphisms of the IL-6, osteocalcin, and vitamin D receptor (VDR) genes, respectively, were associated, alone or in combination, with bone mineral density (BMD) in community-dwelling Japanese women (between 1108 and 1113) or men (between 1116 and 1130) aged 40–79 yr. The −634C→G polymorphism of the IL-6 gene and the 298C→T polymorphism of the osteocalcin gene were associated with BMD in postmenopausal women, with the respective GG and TT genotypes representing risk factors for reduced bone mass. IL-6 and osteocalcin genotypes showed additive effects on BMD for postmenopausal women. The 2C→T polymorphism of the VDR gene was associated with BMD in men, with the CT genotype contributing to reduced BMD. These results suggest that the IL-6 and osteocalcin genes are susceptibility loci for reduced BMD in postmenopausal women and that the VDR gene constitutes such a locus in men. The combined IL-6 and osteocalcin genotypes may prove informative for the assessment of osteoporosis in women.

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Past environmental sun exposure and risk of multiple sclerosis: a role for the Cdx-2 Vitamin D receptor variant in this interaction

Multiple Sclerosis Journal ◽

10.1177/1352458509102459 ◽

2009 ◽

Vol 15 (5) ◽

pp. 563-570 ◽

Cited By ~ 61

Author(s):

JL Dickinson ◽

DI Perera ◽

AF van der Mei ◽

A-L Ponsonby ◽

AM Polanowski ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Vitamin D Receptor ◽

Significant Interaction ◽

Important Determinant ◽

Sun Exposure ◽

Population Based ◽

Vdr Gene ◽

Increased Risk ◽

Group 2

Multiple studies have provided evidence for an association between reduced sun exposure and increased risk of multiple sclerosis (MS), an association likely to be mediated, at least in part, by the vitamin D hormonal pathway. Herein, we examine whether the vitamin D receptor ( VDR), an integral component of this pathway, influences MS risk in a population-based sample where winter sun exposure in early childhood has been found to be an important determinant of MS risk. Three polymorphisms within the VDR gene were genotyped in 136 MS cases and 235 controls, and associations with MS and past sun exposure were examined by logistic regression. No significant univariate associations between the polymorphisms, rs11574010 ( Cdx-2A > G), rs10735810 ( Fok1T > C), or rs731236 ( Taq1C > T) and MS risk were observed. However, a significant interaction was observed between winter sun exposure during childhood, genotype at rs11574010, and MS risk ( P = 0.012), with the ‘G’ allele conferring an increased risk of MS in the low sun exposure group (≤2 h/day). No significant interactions were observed for either rs10735810 or rs731236, after stratification by sun exposure. These data provide support for the involvement of the VDR gene in determining MS risk, an interaction likely to be dependent on past sun exposure.

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The Vitamin D Receptor (VDR) Gene Polymorphisms in Turkish Brain Cancer Patients

BioMed Research International ◽

10.1155/2013/295791 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Bahar Toptaş ◽

Ali Metin Kafadar ◽

Canan Cacina ◽

Saime Turan ◽

Leman Melis Yurdum ◽

...

Keyword(s):

Vitamin D ◽

Cancer Patients ◽

Vitamin D Receptor ◽

Brain Cancer ◽

Gene Polymorphisms ◽

Vdr Gene ◽

Increased Risk ◽

Vdr Gene Polymorphisms ◽

Significant Difference ◽

Healthy Control

Objective. It has been stated that brain cancers are an increasingly serious issue in many parts of the world. The aim of our study was to determine a possible relationship between Vitamin D receptor (VDR) gene polymorphisms and the risk of glioma and meningioma.Methods. We investigated the VDR Taq-I and VDR Fok-I gene polymorphisms in 100 brain cancer patients (including 44 meningioma cases and 56 glioma cases) and 122 age-matched healthy control subjects. This study was performed by polymerase chain reaction-based restriction fragment length polymorphism (RF LP).Results. VDR Fok-I ff genotype was significantly increased in meningioma patients (15.9%) compared with controls (2.5%), and carriers of Fok-I ff genotype had a 6.47-fold increased risk for meningioma cases. There was no significant difference between patients and controls for VDR Taq-I genotypes and alleles.Conclusions. We suggest that VDR Fok-I genotypes might affect the development of meningioma.

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