Are vitamin D deficiency and VDR gene polymorphisms associated with high blood pressure as defined by the ACC/AHA 2017 criteria in postmenopausal women?

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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The effect of VDR gene polymorphisms and vitamin D level on blood pressure, risk of preeclampsia, gestational age, and body mass index

Journal of Cellular Biochemistry ◽

10.1002/jcb.27934 ◽

2018 ◽

Vol 120 (4) ◽

pp. 6441-6448 ◽

Cited By ~ 7

Author(s):

Negin Rezavand ◽

Saba Tabarok ◽

Ziba Rahimi ◽

Asad Vaisi‐Raygani ◽

Ehsan Mohammadi ◽

...

Keyword(s):

Blood Pressure ◽

Body Mass Index ◽

Vitamin D ◽

Body Mass ◽

Gestational Age ◽

Gene Polymorphisms ◽

Vdr Gene ◽

Vdr Gene Polymorphisms ◽

Risk Of Preeclampsia

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Vitamin D and VDR Gene Polymorphisms’ Association with Rheumatoid Arthritis in Lithuanian Population

Medicina ◽

10.3390/medicina57040346 ◽

2021 ◽

Vol 57 (4) ◽

pp. 346

Author(s):

Egle Punceviciene ◽

Justina Gaizevska ◽

Rasa Sabaliauskaite ◽

Lina Venceviciene ◽

Alina Puriene ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Vitamin D ◽

Disease Activity ◽

Vitamin D Deficiency ◽

Gene Polymorphisms ◽

Disease Risk ◽

University Hospital ◽

Healthy Controls ◽

Vdr Gene ◽

Vdr Gene Polymorphisms

Background and Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune, multi-factorial disease, in which environmental and genetic factors play a major role. RA is possibly linked to vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms, and research demonstrates that FokI variant susceptibility is associated with increased disease risk among Caucasians. The aim of this study was to evaluate vitamin D deficiency prevalence and its correlation to RA clinical parameters, and to determine the possible association of VDR gene polymorphisms and RA susceptibility in the Lithuanian population. Materials and Methods: Overall, 206 RA patients and 180 age- and sex-matched healthy controls were enrolled at Vilnius University Hospital Santaros Klinikos after informed consent was obtained. The disease activity score 28 C-reactive protein (DAS28 CRP), rheumatoid arthritis impact of disease (RAID) score, and health assessment questionnaire (HAQ) were recorded in RA patients, and 25(OH)D serum levels were evaluated by chemiluminescent microparticle immunoassay for all subjects. Four VDR gene polymorphisms, BsmI, FokI, ApaI, and TaqI, were assessed using real-time PCR instruments and genotyping assays in both groups. Results: The study registered a high prevalence of 25(OH)D deficiency (<50 nmol/L) in RA patients (61.55% (n = 127)). The mean serum concentration in RA patients (44.96 ± 21.92 (nmol/L)) was significantly lower than in the healthy controls (54.90 ± 22.82 (nmol/L)), p < 0.0001. A significant inverse correlation between vitamin D level, DAS28 CRP, and HAQ scores was confirmed in RA patients, with p < 0.05. Still, there was no significant association between the overall risk of RA disease for any allele or genotype of the four VDR loci tested. Conclusions: The study confirmed that vitamin D deficiency is prevalent among RA patients and the 25(OH)D level is significantly lower compared with healthy controls. Lower vitamin D concentration was related with increased disease activity and disability scores. However, genetic analysis of four VDR polymorphisms did not confer the susceptibility to RA in Lithuanian population.

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Association of Vitamin D Receptor gene polymorphisms with the occurrence of low bone density, osteopenia, and osteoporosis in patients with type 2 diabetes

10.21203/rs.2.20663/v1 ◽

2020 ◽

Author(s):

Maryam Ghodsi ◽

Abbas Ali Keshtkar ◽

Farideh Razi ◽

Mahsa Mohammad Amoli ◽

Ensieh Nasli-Esfahani ◽

...

Keyword(s):

Vitamin D ◽

Bone Density ◽

Vitamin D Deficiency ◽

Vitamin D Receptor ◽

Gene Polymorphisms ◽

Receptor Gene ◽

Vdr Gene ◽

Low Bone Density ◽

Vdr Gene Polymorphisms

Abstract Background Diabetes, osteoporosis, and Vitamin D deficiency are interrelated. The association of the Vitamin D receptor (VDR) gene with bone density is not established in different populations. This study analyze the association between five VDR gene polymorphisms (Fok1 (rs2228570), Taq1 (rs731236), Bsm1 (rs1544410), Apa1 (rs7975232), and EcoRV (rs4516035)) and the occurrence of low bone density (LBD)/osteopenia/osteoporosis in Iranian type 2 diabetics (T2D).Methods This study contained 165 patients with T2D. Separated for gender and polymorphism, crude and adjusted (for age and BMI), logistic regression analysis provided odds ratios (ORs). The most common haplotype was used as the reference for each type of VDR gene polymorphism.Results The occurrence of T2D was 13.03% (165/1266) for the people dwelling in the city of Sanandaj in 2012, until 2013. 13.92% and 81.29% of participants with T2D had osteoporosis and vitamin D deficiency, respectively. In women, tt genotype significantly decreased the risk of LBD/osteopenia/osteoporosis versus Tt genotype, after adjusting for BMI and age (OR=0.18, CI: 0.03-0.97). Conversely, the EE genotype increased the risk of LBD/osteopenia/osteoporosis versus Ee genotype (OR=7.64, CI: 2.03-28.72).Conclusions Among the patients with T2D, Vitamin D deficiency and osteoporosis were prevalent, and some genetic variations in VDR were significantly associated with osteoporosis. In women, a weak protective role in LBD/osteopenia/osteoporosis was found for tt variant of TaqI polymorphism. More importantly, EE variant of EcoRV polymorphism had a strong significant association with increasing the risk of LBD/osteopenia/osteoporosis. Further ethnicity-based cohort studies based on a large study group of T2D patients are recommended.

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Association of Vitamin D Receptor Gene Polymorphisms with Serum Vitamin D Levels in a Greek Rural Population (Velestino Study)

Lifestyle Genomics ◽

10.1159/000514338 ◽

2021 ◽

pp. 1-10

Author(s):

Natalia Divanoglou ◽

Despina Komninou ◽

Eleni A. Stea ◽

Anagnostis Argiriou ◽

Grigorios Papatzikas ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Deficiency ◽

Vitamin D Receptor ◽

Rural Population ◽

Gene Polymorphisms ◽

Molecular Mechanisms ◽

Vdr Gene ◽

Increased Risk ◽

Vitamin D Levels ◽

Vdr Gene Polymorphisms

Background/Aim: An alarming increase in vitamin D deficiency even in sunny regions highlights the need for a better understanding of the genetic background of the vitamin D endocrine system and the molecular mechanisms of gene polymorphisms of the vitamin D receptor (VDR). In this study, the serum levels of 25(OH)D3 were correlated with common VDR polymorphisms (ApaI, BsmI, FokI, and TaqI) in 98 subjects of a Greek homogeneous rural population. Methods: 25(OH)D3 concentration was measured by ultra-HPLC, and the VDR gene polymorphisms were identified by quantitative real-time PCR followed by amplicon high-resolution melting analysis. Results: Subjects carrying either the B BsmI (OR: 0.52, 95% CI: 0.27–0.99) or t TaqI (OR: 2.06, 95%: 1.06–3.99) allele presented twice the risk for developing vitamin D deficiency compared to the reference allele. Moreover, subjects carrying 1, 2, or all 3 of these genotypes (BB/Bb, Tt/tt, and FF) demonstrated 2-fold (OR: 2.04, 95% CI: 0.42–9.92), 3.6-fold (OR: 3.62, 95% CI: 1.07–12.2), and 7-fold (OR: 6.92, 95% CI: 1.68–28.5) increased risk for low 25(OH)D3 levels, respectively. Conclusions: Our findings reveal a cumulative effect of specific VDR gene polymorphisms that may regulate vitamin D concentrations explaining, in part, the paradox of vitamin D deficiency in sunny regions, with important implications for precision medicine.

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Study of vitamin D receptor gene polymorphisms in a cohort of myocardial infarction patients with coronary artery disease

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01959-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Damir Raljević ◽

Viktor Peršić ◽

Elitza Markova-Car ◽

Leon Cindrić ◽

Rajko Miškulin ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Vitamin D ◽

Coronary Artery ◽

Vitamin D Receptor ◽

Gene Polymorphisms ◽

Vdr Gene ◽

Vdr Polymorphism ◽

Vdr Gene Polymorphisms ◽

Vdr Polymorphisms

Abstract Background Vitamin D deficiency is associated with cardiovascular diseases, including coronary artery diseases (CAD). As vitamin D manifests its biological function through its vitamin D receptor (VDR), VDR gene polymorphisms potentially affect VDR functionality and vitamin D activity. Therefore, the objective of this study was to analyze three well-studied VDR gene polymorphisms—Fok1 (rs2228570), BsmI (rs1544410) and Taq1 (rs731236)—in a cohort of CAD patients after acute myocardial infarction. Methods In the presented cross-sectional study, 155 participants with CAD after acute myocardial infarction and 104 participants in a control group without CAD were enrolled. The participants in both groups were Caucasians of European origin. The genotyping of VDR polymorphisms rs2228570, rs1544410 and rs731236 was assessed by RT-PCR. Results The results show an association between the T/T genotype of the BsmI (rs1544410) and the G/G genotype of the Taq1 (rs731236) VDR polymorphism and CAD patients after acute myocardial infarction. There was no association between the Fok1 (rs2228570) VDR polymorphism and CAD patients after acute myocardial infarction. Conclusion The presented results suggest a potential association of the BsmI (rs1544410) and Taq1 (rs731236) VDR polymorphisms with CAD patients after myocardial infarction.

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Retraction Note: Associations between VDR Gene Polymorphisms and Osteoporosis Risk and Bone Mineral Density in Postmenopausal Women: A systematic review and Meta-Analysis

Scientific Reports ◽

10.1038/s41598-021-88654-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Liang Zhang ◽

Xin Yin ◽

Jingcheng Wang ◽

Daolinag Xu ◽

Yongxiang Wang ◽

...

Keyword(s):

Bone Mineral Density ◽

Systematic Review ◽

Postmenopausal Women ◽

Bone Mineral ◽

Gene Polymorphisms ◽

Meta Analysis ◽

Mineral Density ◽

Vdr Gene ◽

Vdr Gene Polymorphisms ◽

Osteoporosis Risk

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-021-88654-1.

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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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