Association between Vitamin D receptor polymorphisms and the rate of bone loss in elderly women—importance of adjusting for dietary and lifestyle factors
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The active metabolite (1, 25-dihydroxycholecalciferol) of vitamin D (25-hydroxycholecalciferol) leads to activation of macrophages and deficiency of vitamin D seems to be involved in the risk of tuberculosis. The effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and may be influenced by polymorphism in the VDR gene. In this study, variation in the VDR gene was investigated in Korean population with tuberculosis.We typed three VDR polymorphisms of restriction endonuclease sites for TaqI, BsmI and FokI in 155 patients with tuberculosis and 105 healthy volunteers.The frequencies of FokI genotypes determined from TB patients were 29.13% for FF, 56.31% for Ff, and 14.56% for ff. We observed 1.4-fold increased prevalence of the Ff genotype in TB patients compared with normal healthy groups (p=0.0857). However, there was no significant association between the genotype groups, TB patient and normal control, for FokI polymorphism. There was also no significant association between VDR gene and tuberculosis in another polymorphism (BsmI and TaqI).Three polymorphisms (TaqI, BsmI and FokI) in the VDR gene do not appear to be responsible for host susceptibility to human tuberculosis in Korean population.
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Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms are involved in a variety of biological processes including cell proliferation, apoptosis, and adhesion in malignant tumors. This study investigated whether vitamin D levels and genetic variations of VDR are risk factors for thyroid cancer.Patients who underwent surgery for differentiated thyroid carcinoma (n=113) and those with benign thyroid pathology (n=150) were genotyped for VDR gene polymorphisms (ApaI, TaqI, FokI, and BsmI) and their 25(OH)D levels were simultaneously measured. Demographic data and histopathologic reports were also acquired for all patients.Vitamin D levels were significantly lower in the thyroid cancer group (p=0.03). FokI and TaqI polymorphisms were more frequent in the thyroid cancer patients (p<0.001). Compared to control, the proportion of the FokI Ff genotype was increased (p<0.0006) and the proportion of the TaqI Tt genotype was also higher among patients with thyroid cancer (p<0.0001). The Ff genotype of FokI was also associated with multifocality, invasive pattern, and risk for local metastasis.The VDR gene polymorphism FokI may be associated with the risk of thyroid cancer and its more aggressive forms.
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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.
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The vitamin D receptor (VDR), a member of the nuclear receptor superfamily of transcriptional regulators, is crucial to calcitriol signalling. VDR is regulated by genetic and environmental factors and it is hypothesised that the response to vitamin D supplementation could be modulated by genetic variants in the VDR gene. The best studied polymorphisms in the VDR gene are Apal (rs7975232), BsmI (rs1544410), Taql (rs731236) and Fokl (rs10735810). We conducted a systematic review and meta-analysis to evaluate the response to vitamin D supplementation according to the BsmI, TaqI, ApaI and FokI polymorphisms. We included studies that analysed the relationship between the response to vitamin D supplementation and the genotypic distribution of these polymorphisms. We included eight studies that enrolled 1038 subjects. The results showed no significant association with the BsmI and ApaI polymorphisms (p = 0.081 and p = 0.63) and that the variant allele (Tt+tt) of the TaqI polymorphism and the FF genotype of the FokI variant were associated with a better response to vitamin D supplementation (p = 0.02 and p < 0.001). In conclusion, the TaqI and FokI polymorphisms could play a role in the modulation of the response to vitamin D supplementation, as they are associated with a better response to supplementation.
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Vitamin D receptor (VDR) gene polymorphisms may influence risk for adenomatous polyps (AP), a benign precursor to colon cancer, via modulation of vitamin D sensitive pathways, including cell proliferation and differentiation. However, results have been mixed and any association remains contentious. Failure to clinically exclude the presence of (AP in control cohorts may contribute to the lack of consensus. Therefore, we assessed the role of the FokI, BsmI, ApaI, and TaqI VDR polymorphisms in modifying risk for AP, adjusting for a range of dietary and lifestyle variables. Blood was collected from colonoscopy patients (n = 258) and VDR polymorphisms assessed by restriction fragment length polymorphism. Dietary habits were estimated from food frequency questionnaires. Odds ratios for AP were calculated by genotype, stratified by sex, and adjusted for age, lifestyle, and dietary factors. FokI was associated with modified risk for AP in males, whereas the BsmI/ApaI/TaqI haplotype was associated with modified risk in females. No interaction was found between VDR variants and vitamin D intake. This study offers novel insight into the potential for VDR genetics to contribute to risk for AP and is the first to demonstrate a sex-specific relationship between these polymorphisms and risk for AP.
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Clinical studies suggested that vitamin D is important in regulating signaling pathways and cellular processes. It exerts this effect through binding to the transcription factor, vitamin D receptor (VDR). Polymorphisms in the VDR gene have been associated with alter function of vitamin D and affect its protective role in many cancers such as colorectal cancer (CRC). In Saudi Arabia, CRC is considered one of the most common and aggressive tumors in both genders. The effect of four polymorphisms (ApaI, TaqI, BsmI, and FokI) in VDR gene was determined and correlated with the CRC progression. The study was conducted on 132 CRC patients and 124 controls who were recruited from King Abdulaziz University Hospital in Jeddah, Saudi Arabia. The gDNA samples were extracted from peripheral blood cells and genotypes were determined with PCR-RFLP and DNA sequencing. The degree of association (χ2), odds ratio (OR), risk ratio (RR), and P values were calculated using Hardy-Weinberg equilibrium equation. Results showed that only heterozygous (Aa) for ApaI increased the risk of CRC (OR=2, RR=3, and P≤0.0001), whereas, for TaqI, heterozygous (Tt) or homozygous (tt) genotype increased the risk of CRC (OR=6, RR=4, and P≤0.0001; OR=3, RR=2, and P=0.2, respectively). For BsmI, this variant showed a significant reduction in CRC risk for heterozygous (Bb) and homozygous (bb) (P values
≤0.0001, respectively). FokI showed no association with CRC risk (P>0.05). The expression of total vitamin D and vitamin D3 in the serum were affected in patients with heterozygous (Aa) genotype for ApaI. In conclusion, the findings provide only limited support for an association between common polymorphisms in VDR and CRC risk. Therefore, more investigations on epigenetic level are required to conclude the probability of using VDR polymorphisms as diagnostic and prognostic markers for CRC.
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The aim of this study was to determine whether vitamin D receptor (VDR) genetic polymorphisms are associated with the susceptibility to pulmonary tuberculosis (PTB).MEDLINE and Embase databases and manual literature searches were used.A meta-analysis was conducted on the associations between the VDR FokI, TaqI, BsmI, and ApaI polymorphisms and PTB susceptibility.A total of 16 studies comprising 3231 patients and 3670 controls met the study inclusion criteria, consisting of 14 studies on the VDR FokI polymorphism, 13 on the VDR TaqI polymorphism, 8 on the VDR BsmI polymorphism, and 5 on the VDR ApaI polymorphism.Meta-analysis of the VDR FokI polymorphism showed no association between PTB and the f allele of the VDR FokI polymorphism (long variant) in all subjects (OR = 1.070, 95%CI = 0.979-1.169,P = 0.134).In contrast, after stratification by ethnicity, meta-analysis indicated that the VDR FokI F allele (short variant) was associated with PTB risk in an East Asian population (OR = 1.507, 95%CI = 1.192-1.906,P = 0.001).Meta-analysis revealed no association between PTB susceptibility and the VDR TaqI t allele in all study subjects (OR = 0.986, 95%CI = 0.839-1.159,P = 0.866) 9119 VDR polymorphisms and tuberculosis ©FUNPEC-RP www.funpecrp.com.brGenetics and Molecular Research 14 (3): 9118-9129 (2015) or in individual ethnic populations.Furthermore, a risk of PTB was not associated with the BsmI and ApaI polymorphisms.This metaanalysis suggested that the VDR FokI polymorphism is associated with a susceptibility to PTB in East Asians.
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