Variations In Vitamin D Receptor Gene Research Articles

Frequency of Healthy Control Genotype of VDR Gene Polymorphisms in the Saudi Population of the Ha'il Region: A Comparative Study with Worldwide Population.

Genetic polymorphisms in the vitamin D receptor (VDR) may influence the biological effects of vitamin D and increase a person's susceptibility to cancer. Previous studies have shown that different ethnic groups exhibit varying frequencies of the VDR gene variants TaqI, ApaI, FokI, and BsmI. However, the allelic distribution of these VDR polymorphisms in the Saudi population of Ha'il region is not sufficiently explored. In this study, efforts were made to ascertain the frequency of VDR polymorphisms in the Saudi population of Ha'il region, and then comparison was made for VDR polymorphism rates with other populations of the world. Allele and genotype frequencies of VDR TaqI, ApaI, BsmI and FokI gene was determined. The frequency distribution for the variant allele of VDR TaqI, ApaI, BsmI and FokI was found to be 70, 33, 50 and 25%, respectively. A significant frequency distribution was found for VDR-TaqI, ApaI and FokI variants in comparison with other populations of the world. Whereas, almost all of the studies dealing with VDR-FokI failed to show substantial difference while comparing with the data reported from the population of Ha'il region of Saudi Arabia. A significant pattern in the frequency of VDR gene variations have been found in the Saudi population of Ha'il region, which may be attributed to ethnic variance. The understanding of the worldwide distribution of VDR markers could help with high-risk screening of those who are exposed to environmental hazards and people of Ha'il region, who are predispose to cancer.

Hereditary Vitamin D-Resistant Rickets (HVDRR) associated SNP variants of vitamin D receptor exhibit malfunctioning at multiple levels

Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily. It is a primary regulator of calcium and phosphate homeostasis required for skeleton and bone mineralization. Vitamin D in active form 1α,25 dihydroxyvitamin-D3 mediates its cellular functions by binding to VDR. Active VDR forms heterodimers with partner RXR (retinoid X receptor) to execute its physiological actions. HVDRR (Hereditary Vitamin D-Resistant Rickets) is a rare genetic disorder that occurs because of generalized resistance to the 1α,25(OH)2D3. HVDRR is caused by the polymorphic variations in VDR gene leading to defective intestinal calcium absorption and mineralization of newly forming bones. Using point and deletion SNPs of VDR we have studied several HVDRR-associated SNP variants for their subcellular dynamics, transcriptional functions, ‘genome bookmarking’, heterodimeric interactions with RXR, and receptor stability. We previously reported that VDR is a ‘mitotic bookmarking factor’ that remains constitutively associated with the mitotic chromatin to inherit ‘transcriptional memory’, however the mechanistic details remained unclear. We document that ‘genome bookmarking’ property by VDR is critically impaired by naturally occurring HVDRR-associated point and deletion variants found in patients. Furthermore, these HVDRR-associated SNP variants of VDR were found to be compromised in transcriptional function, nuclear translocation, protein stability and intermolecular interactions with its heterodimeric partner RXR. Intriguingly, majority of these disease-allied functional defects failed to be rescued by RXR. Our findings suggest that the HVDRR-associated SNP variations influence the normal functioning of the receptor, and this derived understanding may help in the management of disease with precisely designed small molecule modulators.

Relationship between vitamin D receptor gene FokI polymorphism and 25-hydroxyvitamin D levels in apparently healthy Syrians

The vitamin D receptor (VDR) protein has an essential function in regulating serum calcium and 1, 25 dihydroxy vitamin D3. Therefore, variations in VDR gene play an essential role in vitamin D levels.This study aimed to detect the distribution of FokI polymorphism in healthy Syrians and its relation to 25-OH-vitamin D levels.The study included 197 unrelated healthy individuals (Female:131 and Male:66) divided into four groups according to their vitamin D levels: no hypovitaminosis D(G1), vitamin D insufficiency(G2), vitamin D deficiency (G3), and severe vitamin D deficiency (G4). Genotyping for the FokI single nucleotide polymorphism was performed by PCR followed by restriction fragment length polymorphism analysis (RFLP).Frequencies of FF, Ff and ff genotypes were 32.4%, 50% and 17.6%, in G1, 19.6%, 60.8% and 19.6% in G2, 52.1%, 37.5% and 10.4% in G3, and 58%, 37.7% and 4.3% in G4 respectively, with significant differences between the four groups.In conclusion, this study showed a strong correlation between 25-OH-vitamin D levels and FokI polymorphism of the VDR gene in apparently healthy Syrians.

Vitamin D receptor gene polymorphism as a factor of early osteopenia formation in case of a combined course of osteoarthritis and obesity in young people

Objective: to reveal the prognostic-diagnostic significance of polymorphism of vitamin D receptor (VDR) gene G63980A, reference SNP (rs) 1544410, and possible prognostication of the risk of disorders appearance in the structural-functional state of the bone tissue in a combined course of osteoarthritis (OA) and obesity in young people.Methods: the study group included 96 patients at the age of (35.5 ± 0.9) years with OA and obesity, the control group were 96 practically healthy people of the same age and gender, the comparison group consisted of 18 patients with OA and the normal body mass.Obesity was classified after calculation of the body mass (Ketle) index. The functional state of the locomotor system was assessed by the WOMAC scale. The mineral density of the bone tissue was measured with bone densitometer Explorer QDR W (Hologic). Gene polymorphism was investigated in the human genome by the method of polymerase chain reaction. Odds ratio (OR) of the disease development was calculated.Results: severe radiological stages of joints were revealed 2.4 times more frequently in OA combined with obesity than in isolated OA. Osteoporosis was diagnosed in 59.4 % of patients from the study group versus 50 % in the comparison one. In the study group, patients with polymorphic variants of VDR gene, who had the B allele, predominated. The following risk factors for the development of OA were revealed: bone fractures in patients and their family members in the past history, genotype variation in VDR gene, age of the onset of disease under 30 and the radiological stage of OA.Conclusions: clinical-instrumental manifestations of the disease worsen in young patients with OA against a background of obesity. The same patients form osteoporotic disorders as early as during five years of the combined course of the above nosologies. Prognostically unfavourable factors are as follows: the BB variant of VDR gene, fractures in patients and their family members’ past history, manifestation of the disease under 30 years of age and the radiological stage of OA.

Polymorphic Variations in VDR Gene in Saudi Women with and Without Polycystic Ovary Syndrome (PCOS) and Significant Influence of Seven Polymorphic Sites on Anthropometric and Hormonal Parameters.

SummaryBackgroundThis study was designed to evaluate the associations between vitamin D receptor (VDR) gene polymorphisms and biochemical characteristics of Saudi women with polycystic ovary syndrome (PCOS).MethodsSerum levels of LH, FSH, and Vitamin D were measured in 33 women: 16 patients and 17 normal controls (18 to 36 years). DNA was extracted and used for sequencing of the exons of VDR gene using ABI PRISM 3730xi Genetic Analyzer.ResultsWeight, BMI, Vit D, LH and FSH levels were higher in the PCOS patients compared to control group, where Vit D level correlated positively and significantly with FSH, in the control, but showed a negative and non-significant correlation in the PCOS patients. Sequencing results showed extensive polymorphisms in both groups, but the differences in the frequencies were not significant. Demographic and hormonal parameters were compared in the different genotypes of the SNPs. Significant differences were ob served in the values of the studied parameters in rs11168276, rs11168266, rs3858733, rs121909790, rs11168265 and rs731236. Vitamin D level was influenced significantly by the genotypes of rs11168265 (AA) (p=0.008), rs11168276 (AA; p=0.018) and rs731236 (CC; p=0.024).ConclusionVitamin D deficiency does not associate with PCOS in Saudi females. Several SNPs are identified in the VDR gene, in normal and PCOS females, but there is no difference in their frequencies between the two groups. The results show that polymorphism in VDR gene influences certain anthropometric and hormonal parameters in PCOS patients. Further detailed studies are required to confirm the associations between VDR and PCOS.

Associations among two vitamin D receptor (VDR) gene polymorphisms (ApaI and TaqI) in acne vulgaris: A pilot susceptibility study.

Acne vulgaris (AV) pathogenesis is multifactorial. Vitamin D (VitD) plays an important role in sebocytes' differentiation and function. Most VitD functions are mediated by the nuclear VitD receptor (VDR) following binding of its biologically active form (1,25 dihydroxyvitamin D3). Genetic variations in VDR gene may cause significant receptor dysfunction and have been found to be associated with many inflammatory skin diseases. Two adjacent single nucleotide polymorphisms of VDR, ApaI (rs7975232) and TaqI (rs731236), were commonly studied. To evaluate the association between VDR ApaI and TaqI gene polymorphism and AV. This case control study included 30 Egyptian acne patients who attended Dermatology Outpatient Clinic of Al-Zahraa University and Misr University for Science and Technology Hospitals. Thirty age- and sex-matched healthy individuals participated as controls. VDR gene ApaI and TaqI polymorphisms were examined by polymerase chain reaction restriction fragment length polymorphism. Serum 25(OH)D was measured in all participants. Patients had significant decrease in ApaI A allele and AATT combined genotype (60%, 3.3%) than controls (78.3%, 20%), respectively, and significant increase in TaqI tt genotype and t allele (46.7%, 63.3%) than controls (13.3%, 41.7%), respectively. Patients showed significantly lower serum 25(OH)D3 concentration than controls. Polymorphisms of ApaI and TaqI may have a role in the pathogenesis of AV as A allele and AATT combined genotype could be considered protective against acne development and tt genotype and t allele may increase the risk of AV development. VitD deficiency can be considered as a risk factor for AV development.

Polymorphic Variations in VDR gene in Saudi Women with and without Polycystic Ovary Syndrome (PCOS) and Significant Influence of Seven Polymorphic Sites on Anthropometric and Hormonal Parameters

Summary Background: This study was designed to evaluate the associations between vitamin D receptor (VDR) gene polymorphisms and biochemical characteristics of Saudi women with polycystic ovary syndrome (PCOS). Methods: Serum levels of LH, FSH, and Vitamin D were measured in 33 women: 16 patients and 17 normal controls (18 to 36 years). DNA was extracted and used for sequencing of the exons of VDR gene using ABI PRISM 3730xi Genetic Analyzer. Results: Weight, BMI, Vit D, LH and FSH levels were higher in the PCOS patients compared to control group, where Vit D level correlated positively and significantly with FSH, in the control, but showed a negative and non-significant correlation in the PCOS patients. Sequencing results showed extensive polymorphisms in both groups, but the differences in the frequencies were not significant. Demographic and hormonal parameters were compared in the different genotypes of the SNPs. Significant differences were ob served in the values of the studied parameters in rs11168276, rs2228570, rs11168266, rs3858733, rs121909790, rs11168265 and rs731236. Vitamin D level was influenced significantly by the genotypes of rs11168265 (AA) (p=0.008), rs11168276 (AA; p=0.018) and rs731236 (CC; p=0.024). Conclusion: Vitamin D deficiency does not associate with PCOS in Saudi females. Several SNPs are identified in the VDR gene, in normal and PCOS females, but there is no difference in their frequencies between the two groups. The results show that polymorphism in VDR gene influences certain anthropometric and hormonal parameters in PCOS patients. Further detailed studies are required to confirm the associations between VDR and PCOS.

Vitamin D: relevance in dental practice

The potential role of VDR gene variations in modulating periodontal susceptibility have been a subject of scientific investigations. The aim of this paper is to perform a literature review of the potential correlation between Vitamin D Receptor (VDR) gene polymorphisms and periodontal disease. A PubMed literature search was made using "vitamin d receptor polymorphisms periodontal disease" as keys words. Only clinical studies in "Humans" as species and "English" as language were considered. Titles and abstracts of all identified records were examined to determine if the candidate articles contained sufficient information on the association of the VDR polymorphisms and the risk of development periodontal disease. Vitamin D may affect the risk of developing periodontal disease via an effect on bone mineral density or via immunomodulatory effects. There are scientific evidences about the correlation between some VDR polymorphisms, periodontitis and bone metabolism. The use of new simple and economics diagnostic techniques of genetic screening, allows to the dental specialists to identify periodontal patients with possible decreased bone mineral density. The complete acquisition of awareness by dentists of the strong relationship between skeletal bone density with periodontal health and osteointegrated implant success, could open a new therapeutic approach for periodontists with an important role in the early detection of osteoporosis and a better patient compliance of the periodontal therapy.

Relationship of BsmI polymorphism of vitamin D receptor gene with left ventricular hypertrophy and atherosclerosis in hemodialysis patients

Background. Left ventricular hypertrophy (LVH) is a common manifestation of cardiovascular disease and has an important prognostic value in patients with end-stage renal disease (ESRD). Vitamin D receptor (VDR) has been intensively investigated, and one of these (BsmI) already has been associated with survival in the dialysis population. Objective. The aim of this study was to investigate the role of VDR polymorphism (BsmI) on the development of ventricular hypertrophy and atherosclerosis in hemodialysis patients. Subject and methods. The subjects were 80 patients with end-stage renal disease on maintenance hemodialysis, and 40 healthy controls. Clinical and laboratory parameters, including genetic variation in VDR gene (BsmI), were assessed. In addition, echocardiography and intima-media thickness were performed for all subjects. Results. There was no significant difference in the distribution of BsmI genotypes either in patients or in the control group. The frequency of the B allele of BsmI polymorphism (41.6%) in dialysis patients was similar to that of healthy control subjects (39.2%). Patients with BB genotype had significantly lower serum concentrations of 25-hydroxy vitamin D compared to both Bb and bb genotypes. The number of B alleles was positively correlated with left ventricular mass index (LVMI), but not with intima-media thickness. Conclusion. These results suggest that the B alleles of the BsmI polymorphism could be considered as novel markers of altered vitamin D signaling in ESRD patients, and this alteration in BB genotype produces an increase in left ventricle mass.

Potential association of vitamin D receptor polymorphism Taq1 with multiple sclerosis

Background: The environmental influence of sun exposure and vitamin D in particular and its implication with multiple sclerosis (MS) has recently received considerable attention. Current evidence based on genetic and epidemiological studies indicate that vitamin D is implicated in the aetiology of this disease. Methods: We examined two common variants in the vitamin D receptor (VDR) gene in 1153 trio families and 726 cases and 604 controls. We also examined epistatic interactions between the VDR SNPs rs731236 and rs2228570 with the tagging single nucleotide polymorphism (SNP) rs3135388 for the HLA-DRB*1501 locus containing a highly conserved vitamin D responsive element within its promoter region. Results: We found weak evidence for an association between the rs731236C allele and MS, while there was no direct association with rs2228570. When examining the interaction between the VDR gene variations and the DRB1*1501 tagging SNP a more complex relationship was observed. Although the interaction was not statistically significant, there appeared to be a trend of increasing risk of MS in participants who were homozygous for the HLA-DRB1*1501 allele in association with the more active form of the VDR (Fok1). Conclusion: We have identified weak evidence of an association between a common variation within the VDR gene and MS, in the largest study reported to date of this candidate gene. There appears to be a relationship between polymorphisms in the VDR and the risk of MS, which is potentially modified by HLA-DRB1*1501.