Vitamin D Receptor TaqI Genotypes Research Articles

Association of Vitamin D receptor (TaqI, BsmI, and FokI) polymorphisms with prediabetes and Type 2 diabetes in Asian Indians

Background: Vitamin D deficiency is known to be involved in the development of insulin resistance and type 2 diabetes (T2D), and the functions of Vitamin D are mediated through Vitamin D receptor (VDR). Only a few reports are available in the Asian Indian population highlighting the role of VDR polymorphism in diabetes. We aimed to investigate the association of VDR gene polymorphisms (TaqI, BsmI and FokI) with prediabetes (PD) and T2D and their relationship with anthropometric and biochemical parameters in Asian Indians. Subjects and Methods: In this study, 454 participants including 147 with normal glucose tolerance (NGT), 145 with PD, and 162 with T2D were enrolled in this study. Genetic variants of the VDR were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Anthropometric measurements were done in all participants. Results: The most common genotypes for TaqI, BsmI, and FokI were TC, GA, and CC, respectively. The allele distribution of TaqI differed significantly when compared between NGT and T2D group. A significant protection was shown against T2 in VDR TaqI genotypes after adjusting for age, gender, and Body Mass Index. The levels of homeostatic model assessment for insulin resistance, fasting insulin, and the waist-hip ratio were significantly higher in TT genotype when compared with TC + CC genotype of TaqI polymorphism in NGT. In PD group, the levels of serum cholesterol and low-density lipoprotein cholesterol were significantly higher in AA genotype when compared with GA + GG genotype in BsmI polymorphism. Conclusions: The study indicates VDR TaqI, and BsmI polymorphisms seem to influence anthropometric and biochemical parameters, and in particular, VDR TaqI polymorphism offers protection against T2D in Asian Indians.

Relationship between vitamin D receptor gene polymorphism and susceptibility to chronic kidney disease and periodontal disease in community-dwelling elderly.

The aim of this study was to investigate the possible correlation between vitamin D receptor (VDR) gene polymorphism and susceptibility to chronic kidney disease (CKD) and periodontal disease. This study analysed 345 participants, who were all 79years of age. Kidney function levels were determined based on the estimated glomerular filtration rate (eGFR; non-reduced function: ≥60 and reduced function: <60mlmin-1 1.73m-2 ). VDR TaqI genotyping was also studied. We calculated the periodontal inflamed surface area (PISA). After classifying participants into quartile groups according to eGFR or PISA values, the subjects were then split into two groups (highest quartile versus the other three groups combined). Multiple logistic regression analysis was performed to evaluate the odds ratios between the eGFR and VDR TaqI genotype with the different PISA groups. The eGFR was set as the dependent variable while the VDR TaqI genotype, HbA1C, gender, smoking habits and body mass index were defined as independent variables. A significant association was observed between the VDR TaqI genotype and eGFR in the PISA high group (odds ratio=3.97, p=.027). Study results suggest that VDR TaqI genotype might be associated with CKD during inflammatory conditions caused by periodontal disease.

Vitamin D receptor gene TaqI single nucleotide polymorphism is not associated with lead levels in maternal and umbilical cord blood

Purpose: We aimed to investigate the association of vitamin D receptor (VDR) gene TaqI single nucleotide polymorphism (SNPs) with serum lead (Pb) levels in maternal and umbilical cord blood.Materials and methods: Eighty-one patients who lived in Konya, Turkey for the last 3 years and had delivery at Başkent University Konya Hospital in 2016 were included in this study. Venous blood samples were drawn from each volunteer immediately before giving birth to determine the maternal Pb levels and VDR SNPs. Additionally, umbilical cord blood samples were collected from the umbilical vein into tube with EDTA as an anticoagulant immediately after birth to determine Pb levels of the fetus.Results: The median level of Pb in the maternal blood was 29.00 (Interquartile Range (IQR) = 16.35) μg/L and the median Pb level in the cord blood was 22.50 (IQR = 9.75) μg/L. Blood Pb level of women living in the urban area was significantly higher than in those living in the rural area (Z = 2.118; p = .034). There was a very strong positive correlation between the Pb levels in the maternal blood and in the umbilical cord blood (ρ = 0.825, p < .001, respectively). Regarding VDR SNPs, “TT”, “TC”, and “CC” VDR TaqI genotypes were observed in 28 (34.6%), 45 (55.5%), and eight samples (9.9%), respectively. Pb levels in maternal and cord blood were higher in women with the “CC” VDR TaqI genotype; however, there was no statistically significant difference (p > .05).Conclusions: Although women with the “CC” VDR TaqI genotype had higher maternal and cord blood Pb levels, this was statistically insignificant and therefore, VDR TaqI SNPs did not significantly affect maternal and umbilical cord blood Pb levels.

Association between Serum 25-hydroxy Vitamin D Concentration and TaqI Vitamin D Receptor Gene Polymorphism among Jordanian Females with Breast Cancer.

Background:Breast cancer is the most common type of cancer among females. Genetic polymorphisms might have a role in carcinogenesis. The aim of this study was to determine whether C to T base substitution within TaqI Vitamin D receptor (VDR) gene (rs731236) in exon 9 was a risk factor among patients with breast cancer.Methods:Peripheral blood was drawn from 122 Jordanian breast cancer patients and 100 healthy Jordanian volunteers in Al-Basheer Hospital during the summer months (from June to November of 2013, 2014, and 2015). DNA was amplified using polymerase chain reaction (PCR), followed by TaqI restriction enzyme digestion. Quantification of serum 25-hydroxy Vitamin D (25[OH]D) level was determined by competitive immunoassay Elecsys.Results:Genotypic frequencies for TaqI TT, Tt, and tt genotypes were 41%, 46%, and 13% for breast cancer compared to 42%, 50%, and 8% for control, respectively. Vitamin D serum level was significantly lower in the breast cancer patients (8.1 ± 0.3 ng/ml) compared to the control group (21.2 ± 0.6 ng/ml; P = 0.001). This study showed an inverse association between 25(OH)D serum level and breast cancer risk (odds ratio [OR], 22.72, 95% confidence interval [CI], 10.06–51.29).Conclusions:An inverse association was found between 25(OH)D serum level and breast cancer risk. Statistical difference was also found between different VDR TaqI genotypes and circulating levels of 25(OH)D among Jordanian females with breast cancer.

Association between vitamin D receptor ApaI and TaqI gene polymorphisms and gestational diabetes mellitus in an Iranian pregnant women population

It has been proposed that variants of the nuclear vitamin D receptor (VDR) gene are associated with a susceptibility to type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM). Our study was aimed to evaluate a possible association between the VDR ApaI (rs7975232) and TaqI (rs731236) gene polymorphisms and susceptibility to GDM in an Iranian pregnant women population. This case–control study was performed on a population of pregnant Iranian women, including 157 GDM and 157 non-GDM subjects.VDR ApaI and TaqI polymorphisms were assessed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Our finding showed that the genotypes frequency of VDR ApaI polymorphism was significantly different between GDM and non-GDM groups (χ2=8.5, P=0.014). The CC genotype increased the risk of GDM as compared to the AA genotype (AA vs.CC, OR=2.996, 95% CI=1.278–7.022, P=0.012). The genotype and allele frequencies of VDR TaqI polymorphism were significantly different between GDM and non-GDM subjects (χ2=7.27, P=0.026, χ2=4.08, P=0.043 respectively). A significant protection was shown against GDM in VDR TaqI genotypes and allele (TT vs.TC, OR=0.523, 95% CI=0.23–0.84, P=0.007, TT vs. TC+CC, OR=0.546, 95% CI=0.35–0.86, P=0.009, T vs. C, OR=0.711, 95% CI=0.511–0.99, P=0.043). In conclusion, our findings show a significant association between VDR ApaI and TaqI gene polymorphisms and the GDM at the investigated loci.

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

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.

Association Between Vitamin D Receptor Gene Polymorphisms and Severe Chronic Periodontitis in a Chinese Population

Chronic periodontitis (CP) exhibits inflammation and alveolar bone loss, and severe forms of periodontitis are suggested to have a genetic basis. Vitamin D receptor (VDR) regulates bone metabolism and inflammation-related genes, and single nucleotide polymorphisms (SNPs) in the VDR gene may affect the functional activity of the VDR protein in CP. Therefore, the aim of this study was to investigate the association between VDR SNPs and severe CP in a Chinese population. DNA was obtained from 107 patients with severe CP and 121 control subjects. The BsmI, TaqI, ApaI, and FokI SNPs of VDR genes were investigated by restriction fragment length polymorphism of polymerase chain reaction (PCR) products. The digested PCR products were electrophoresed on an 8% polyacrylamide gel and developed by the DNA silver staining method. The distribution of VDR TaqI genotypes and alleles between the two groups was significantly different (P = 0.019 and P = 0.039, respectively). The TT genotype and T allele seemed to increase the susceptibility of severe CP (odds ratio, 2.75; 95% confidence interval [CI]: 1.17 to 6.47; odds ratio, 2.28, 95% CI: 1.02 to 5.06, respectively) in Chinese populations. There was no significant difference in the genotype distribution or the allele frequencies of VDR BsmI, ApaI, or FokI between the two groups. TaqI SNP of VDR gene might be associated with severe CP in Chinese patients.

Circulating Vitamin D Metabolites, Polymorphism in Vitamin D Receptor, and Colorectal Adenoma Risk

Abstract Objective: Vitamin D is a potential agent for the prevention of colorectal cancer possibly through mechanisms mediated by the vitamin D receptor (VDR). We investigated the association of circulating vitamin D metabolites and a genetic variant of the VDR gene with advanced colorectal adenoma, a precursor lesion of colorectal cancer. Methods: Cases with advanced adenoma of the distal large bowel and gender- and ethnicity-matched controls with a negative sigmoidoscopy were randomly selected from participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. Genotype analysis of the VDR TaqI polymorphism was completed on 763 cases and 774 controls. Serum levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured in a subset of 394 cases and 397 controls. Results: Serum levels of 25(OH)D were inversely associated with advanced adenoma risk in women but not in men. Comparing those in the highest quintile with those in the lowest quintile, the risk for advanced adenoma decreased by 73% in women [odds ratio (OR) = 0.27, 95% confidence interval (95% CI) = 0.11–0.69; P for trend = 0.0002], while the risk did not decrease in men (OR = 1.10, 95% CI = 0.60–2.05; P for trend = 0.85). In women, 25(OH)D levels were significantly higher in current users of hormone replacement therapy (HRT) than in former or never HRT users. Neither serum 1,25(OH)2D nor VDR TaqI genotype was associated with advanced adenoma risk. Conclusion: Higher serum 25(OH)D levels were associated with decreased adenoma risk. Serum 1,25(OH)2D and VDR TaqI genotype were not associated with adenoma risk.

Vitamin D Receptor Alleles, Bone Mineral Density and Turnover in Postmenopausal Osteoporotic and Healthy Women

Objective: Vitamin D receptor (VDR) gene polymorphisms and bone metabolic markers were investigated as potential genetic markers for osteoporosis in postmenopausal Turkish women. The relationship between their VDR gene polymorphisms and bone states was determined. Materials and Methods: Restriction fragment length polymorphisms at the VDR gene locus (i.e., for BsmI, ApaI, and TaqI) was investigated in 75 postmenopausal osteoporotic (53.16 ± 1.31 years) and 66 healthy (52.62 ± 1.69 years) Turkish women and the genotypes were related to bone mineral density (BMD) at femoral neck (FN), lumbar spine (L1–4), trochanter, Ward’s triangle (Ward’s) and metabolic parameters of bone turnover. Results: In osteoporotic women, TaqI genotype-related differences of the VDR gene were found to be significant at all BMD sites; TT genotype had higher L1–4 BMD values than Tt and tt (p < 0.05); tt genotype had significantly lower BMD at FN (p < 0.05), trochanter (p < 0.01), and Ward’s (p < 0.05) compared to TT genotype. The tt genotype was found to be associated with higher (p < 0.05) serum osteocalcin levels compared to Tt and TT genotypes in the osteoporotic women, whereas no such association was found for the healthy women. Conclusion: Our data showed an association between VDR TaqI genotype and BMD at the FN, L1–4, trochanter and Ward’s triangle in nonobese postmenopausal osteoporotic women. Thus the VDR gene Taql polymorphism modulates differences in BMD in the postmenopausal osteoporotic women.

The role of vitamin D receptor gene polymorphisms in the susceptibility to prostate cancer of a southern European population.

Epidemiological data indicate a relationship between ultraviolet radiation, vitamin D, and prostate cancer risk. Antiproliferative effects of vitamin D require the expression of the nuclear vitamin D receptor (VDR). A three-fold increase in prostate cancer risk associated with the less active vitamin D receptor allele (the T allele from VDR TaqI polymorphism at codon 352) was reported. The role of VDR genotypes in the susceptibility to prostate cancer has not yet been studied in populations of southern Europe. In the present study, we determined VDR TaqI genotypes in Portuguese prostate cancer cases ( n = 163) and controls ( n = 211), a southern European population. When cases were compared with controls, we found an association of VDR T allele with prostate cancer risk (odds ratio [OR] = 1.87, 95% confidence interval [CI] 1.02-3.37; P = 0.035). This association was confirmed using logistic regression analysis (OR = 2.11, 95% CI 1.15-3.88; P = 0.015) and in particular associated to risk of prostate cancer onset in men over the age of 66 years (OR = 2.36, 95% CI 1.05-5.29; P = 0.036). Fifty percent of cases older than 66 years could be attributed to the influence of this risk factor. Our results indicate that the contribution of VDR genotypes to prostate cancer susceptibility might depend on the population studied and its geographic localization, and that VDR genotypes are important in the definition of the genetic risk profile of populations of southern Europe.