Variants in the vitamin D receptor gene and asthma.
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ABSTRACT:
SUBMITTER: Wjst M
PROVIDER: S-EPMC546000 | biostudies-literature | 2005
REPOSITORIES: biostudies-literature
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<h4>Background</h4>Early lifetime exposure to dietary or supplementary vitamin D has been predicted to be a risk factor for later allergy. Twin studies suggest that response to vitamin D exposure might be influenced by genetic factors. As these effects are primarily mediated through the vitamin D receptor (VDR), single base variants in this gene may be risk factors for asthma or allergy.<h4>Results</h4>951 individuals from 224 pedigrees with at least 2 asthmatic children were analyzed for 13 SNP ...[more]
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Project description:We conducted the systematic review to investigate the potential relationship between the vitamin polymorphisms of D receptor (VDR) gene and childhood asthma. Relevant studies researching on VDR polymorphisms and asthma susceptibility were searched throughout Embase, PubMed, China Science and technology journal database (CQVIP), etc. till 12 April, 2021. We calculated the pooled odds ratios (OR) and its 95% confidence interval (CI) using RevMan 5.3 software and Stata 11.0. FokI (rs2228570) could significantly affect childhood asthma risk across co dominant model (Ff vs. FF: OR (95%CI) = 0.82 (0.65, 1.02), P = 0.071) and dominant model (ff+Ff vs. FF: OR (95%CI) = 0.77 (0.63, 0.95), P = 0.016), especially among Caucasians in additive model (f vs. F: OR (95%CI) = 0.63 (0.43, 0.92), P = 0.015) and dominant model (ff+Ff vs. FF: OR (95%CI) = 0.67 (0.51, 0.88), P = 0.004). TaqI (rs731236) was significantly related with childhood asthma in additive model (t vs. T: OR (95%CI) = 0.45 (0.23, 0.89), P = 0.022), co dominant model (Tt vs. TT: OR (95%CI) = 0.36 (0.17, 0.77), P = 0.009), and dominant model (tt+Tt vs. TT: OR (95%CI) = 0.36 (0.15, 0.87), P = 0.024) among Asian, as well as population-based subgroup in co dominant model (Tt vs. TT: OR (95%CI) = 0.53 (0.31, 0.94), P = 0.029). However, no evidence supported the role of ApaI (rs7975232) and BsmI (rs1544410) polymorphisms in childhood asthma. FokI and TaqI polymorphisms were found to be related with the susceptibility of childhood asthma. However, it seems that ApaI and BsmI polymorphisms are not related with childhood asthma susceptibility.
| S-EPMC9010509 | biostudies-literature
Project description:BackgroundThe effects of vitamin D are exerted by interaction with the vitamin D receptor (VDR) and vitamin D binding protein (VDBP). Polymorphisms in VDR or VDBP genes may affect vitamin D levels, influencing the pathogenesis of asthma and atopy. The aim of this study was to investigate the possible association of VDR and VDBP gene single-nucleotide polymorphisms (SNP), 25-hydroxyvitamin D (25(OH)D), blood eosinophils and total IgE level in subjects with asthma in comparison with healthy individuals.MethodsThis case-control study enrolled 63 subjects with asthma (45 allergic and 18 non-allergic) and 32 healthy subjects were involved in the study. Sensitization of subjects to inhaled allergens was determined by a skin prick test, lung function was evaluated by spirometry. Blood eosinophil count was determined by standard methods. Serum 25(OH)D and total IgE levels were evaluated by ELISA. Polymorphisms in the VDR and VDBP genes on the 12q13.11 and 4q13.3 chromosomal region were analyzed using TaqMan SNP Genotyping Assay probes.ResultsIn asthma patients with vitamin D deficiency (< 20 ng/ml) the allele G of rs11168293 of VDR was more common than in those having insufficiency (20-30 ng/ml) of vitamin D (63% and 31%, p < 0.05). Moreover, asthmatic subject with rs11168293 G allele has significant higher blood eosinophil count compared to asthmatic without the rs11168293 G allele (8.5 ± 12.3% vs. 5.1 ± 1.5%, p < 0.05). Significantly higher IgE level was found in subjects with allergic asthma with the allele A of rs7041 on VDBP gene than in those without this allele (540 ± 110 and 240 ± 80 IU/ml, p < 0.05).ConclusionsThe association of polymorphisms in VDBP and VDR gene, the rs11168293 G allele and the rs7041 A allele, with 25(OH)D, blood eosinophil and total IgE level in asthma, let us suggest that vitamin D, VDR and VDBP gene polymorphisms are important in pathogenesis of asthma despite its form in relation to atopy.
| S-EPMC10324267 | biostudies-literature
Project description:Vitamin D receptor (VDR) gene variants have been variably associated with risk of colon cancer in epidemiologic studies. We sought to further clarify the relationship between colon cancer and three single-nucleotide polymorphisms (SNPs) in the VDR gene (Cdx-2, FokI and TaqI) in a population-based case-control study of 250 incident cases and 246 controls. Colon cancer cases were more frequently homozygous for the Cdx-2 A allele (9.2 versus 4.1%, P = 0.06). Cdx-2 AA homozygotes were at increased risk with an unadjusted odds ratio (OR) of 2.47 [95% confidence interval (CI): 1.13-5.37, P = 0.022]; adjustment for age, sex, body mass index (BMI), non-steroidal anti-inflammatory use and family history of colorectal cancer yielded an OR of 2.27 (CI: 0.95-5.41, P = 0.065). Carriers of the FokI TT genotype were also at increased risk with an adjusted OR of 1.87 (CI: 1.03-3.38, P = 0.038). Haplotype analyses showed significant increased colon cancer risk for carriers of the Cdx-2-FokI A-T haplotype and the FokI-TaqI T-G haplotype. The three-SNP Cdx-2-FokI-TaqI (A-T-G) haplotype showed a similar association with an adjusted OR of 3.63 (CI: 1.01-13.07). A strong positive association was observed for the Cdx-2 variant among individuals with low BMI or low waist circumference. Our results suggest that genetic variation at the VDR locus, in particular Cdx-2 and FokI SNPs, may influence colon cancer risk and these associations may be modified by adiposity.
| S-EPMC2722851 | biostudies-literature
Project description:Background:Recent reports have suggested that lower vitamin D serum levels are associated with susceptibility to and severity of asthma in different white populations, which may be due to a lack of sunlight exposure, genetic polymorphism of vitamin D pathway genes, and dietary intake. We investigated the associations between vitamin D concentration, genetic polymorphism of the vitamin D receptor (VDR), and asthma traits in Mongolian and Taiwanese populations that inhabited two different geographical areas. Methods:In total, 328 Han Taiwanese subjects and 381 Mongolian subjects were enrolled, and their vitamin D serum levels assayed. Genomic DNA of 178 Han Taiwanese subjects and 90 Mongolian subjects was obtained from blood samples. Single-nucleotide polymorphisms (SNPs) of VDR, ApaI (rs7975232), TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570), were selected for genotyping. Logistic regression analyses were performed to detect an association between allergic asthma status and the interaction of the VDR SNP and serum vitamin D concentration in the case-control samples. Results:We observed a significantly lower vitamin D level in the Mongolian subjects as compared with the Taiwanese population. In particular, in the population under 14 years of age, the serum vitamin D level was significantly higher in the Taiwanese population, in both non-asthmatic and asthmatic subjects, than in the Mongolian non-asthmatic and asthmatic subjects, respectively (P < 0.01). Moreover, the vitamin D level in the asthmatic children was significantly lower than that in the non-asthmatic children in both the Taiwanese and Mongolian populations (P < 0.01, respectively). Furthermore, we found that the rs2228570 genotype (OR, 3.763) of the VDR SNP and the vitamin D concentration (lower than 40 ng/ml, OR: 38.938) both contribute to increased susceptibility to bronchial asthma. Conclusion:Our results demonstrated an association between vitamin D concentration and the risk of asthma in two populations of differing ethnicity living in different geographical areas. This information implies a potential role of vitamin D in the prevention and treatment of asthma worldwide.
| S-EPMC6838943 | biostudies-literature
Project description:The vitamin D prophylaxis of rickets in pregnant women and newborns may play a role in early allergic sensitization. We now asked if an already diseased population may have inherited genetic variants in the vitamin D turnover or signalling pathway. Serum levels of calcidiol (25-OH-D3) and calcitriol (1,25-(OH)2-D3) were retrospectively assessed in 872 participants of the German Asthma Family Study. 96 DNA single base variants in 13 different genes were genotyped with MALDI-TOF and a bead array system. At least one positive SNP with a TDT of p < 0.05 for asthma or total IgE and calcidiol or calcitriol was seen in IL10, GC, IL12B, CYP2R1, IL4R, and CYP24A1. Consistent strong genotypic association could not be observed. Haplotype association were found only for CYP24A1, the main calcidiol degrading enzyme, where a frequent 5-point-haplotype was associated with asthma (p = 0.00063), total IgE (p = 0.0014), calcidiol (p = 0.0043) and calcitriol (p = 0.0046). Genetic analysis of biological pathways seem to be a promising approach where this may be a first entry point into effects of a polygenic inherited vitamin D sensitivity that may affect also other metabolic, immunological and cancerous diseases.
| S-EPMC1508148 | biostudies-literature
Project description: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.
| S-EPMC8929051 | biostudies-literature
Project description:BackgroundThe genetic mechanisms underlying asthma remain unclear. Increased permeability of the microvasculature is a feature of asthma, and the sphingosine-1-phosphate receptor (S1PR1) is an essential participant regulating lung vascular integrity and responses to lung inflammation.ObjectiveWe explored the contribution of polymorphisms in the S1PR1 gene to asthma susceptibility.MethodsA combination of gene resequencing for single nucleotide polymorphism (SNP) discovery, case-control association, functional evaluation of associated SNPs, and protein immunochemistry studies was used.ResultsImmunohistochemistry studies demonstrated significantly decreased S1PR1 protein expression in pulmonary vessels in lungs of asthmatic patients compared with those of nonasthmatic subjects (P < .05). Direct DNA sequencing of 27 multiethnic samples identified 39 S1PR1 variants (18 novel SNPs). Association studies were performed based on genotyping results from cosmopolitan tagging SNPs in 3 case-control cohorts from Chicago and New York totaling 1,061 subjects (502 cases and 559 control subjects). The promoter SNP rs2038366 (-1557G/T) was found to be associated with asthma (P = .03) in European Americans. In African Americans an association was found for both asthma and severe asthma for intronic SNP rs3753194 (c.-164+170A/G; P = .006 and P = .040, respectively) and for promoter SNP rs59317557 (-532C/G) with severe asthma (P = .028). Consistent with predicted in silico functionality, alleles of the promoter SNPs rs2038366 (-1557G/T) and rs59317557 (-532C/G) influenced the activity of a luciferase S1PR1 reporter vector in transfected endothelial cells exposed to growth factors (epidermal growth factor, platelet-derived growth factor, and vascular endothelial growth factor) known to be increased in asthmatic airways.ConclusionThese data provide strong support for a role for S1PR1 gene variants in asthma susceptibility and severity.
| S-EPMC3495167 | biostudies-literature
Project description:BACKGROUND:Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-age women. Multiple susceptible gene as well as environmental factors and their interaction each other are contributed to the PCOS risk. Several case-control studies have researched the associations of the vitamin D receptor gene (VDR) polymorphisms with PCOS susceptibility, but the jury is still out. Here, we carried out a meta-analysis to clarify polymorphisms between ApaI (C/A) (rs7975232), BsmI (G/A) (rs1544410), FokI (C/T) (rs10735810), TaqI (T/C) (rs731236) and Tru9I (G/A) (rs757343) in the VDR gene and PCOS susceptibility based on relative lager sample size. METHODS:English database of PubMed and Embase, and Chinese database of Wanfang and China National Knowledge Infrastructure (CNKI) databases were retrivaled for the relationship between VDR gene variates and PCOS susceptibility published before 31th, May 2018. Crude odds ratios (ORs) and its 95% confidence intervals (95% CIs) in different comparisons were used to detected the strength of the association. All the statistical analyses of the present meta-analysis were performed by STATA version 12.0 software. RESULTS:Totally, 3587 (PCOS group 1922; control group 1665) participants from 13 studies were included which met our inclusion criteria. A statistically significant association between VDR ApaI (rs7975232) polymorphism and PCOS susceptibility (C vs. A: OR?=?1.19, 95%CI?=?1.06~1.34, P?=?0.004) was found in the overall population. After stratified by ethnicity, we showed that there is a significant association between VDR ApaI (rs7975232) polymorphism and susceptibility to PCOS in the Asian (C vs. A: OR?=?1.21, 95%CI?=?1.04~1.42, P?=?0.016) population, but this association was not found in the Caucasian population. Additionally, a significant relationship between VDR BsmI (rs1544410) variates with PCOS susceptibility in the Asian (G vs. A: OR?=?1.27, 95%CI?=?1.06~1.53, P?=?0.011) population, but this association was not found in the Caucasian population. We didn't find any association between VDR FokI (rs2228570), VDR TaqI (rs731236), VDR Tru9I (rs757343) and PCOS susceptibility in the overall and the subgroup populations. CONCLUSIONS:Our findings demonstrated that VDR ApaI (rs7975232) and VDR BsmI (rs1544410) polymorphisms are correlated with susceptibility to PCOS in the Asian population and VDR TaqI (rs731236), VDR FokI (rs2228570), VDR Tru9I (rs757343) did not reveal a relationship with the PCOS susceptibility.
| S-EPMC6376757 | biostudies-literature
Project description:BackgroundPolymorphisms in the vitamin D receptor (VDR) gene have been studied in immune-related disorders either as independent contributors or in combination with vitamin D concentration. Vitamin D and VDR have been independently linked to asthma susceptibility. We investigated whether VDR variants were associated independently or in relation to vitamin D levels with asthma in Cypriot adolescents.MethodsWe studied 190 current wheezers, 69 of which were categorized as active asthmatics and 671 healthy controls. We determined three VDR genotypes (BsmI, TaqI, ApaI) and measured serum 25(OH)D levels. Logistic regression and stratified analyses by the presence of hypovitaminosis D (≤20 ng/ml) were used to evaluate the association of the VDR variants with asthma.ResultsThe distribution of TaqI genotypes was significantly different between controls and current wheezers (p = 0.030) or active asthmatics (p = 0.014). The tt genotype was over-represented in wheezers (19.2 %) and asthmatics (21.3 %) compared to respective controls (12.9 %). No difference was observed between controls, current wheezers and active asthmatics in the genotypic distribution of BsmI and ApaI polymorphic sites. After stratification by the presence of hypovitaminosis D, a significant association was detected between tt genotype of TaqI polymorphism with wheezing (OR: 1.97, 95 % CI: 1.12, 3.46) and asthma (OR: 2.37, 95CI%: 1.02, 5.52) only in those with normal vitamin D levels (>20 ng/ml) but not in subjects with low vitamin D.ConclusionsThe minor TaqI genotype of VDR is associated with asthma in Cypriot adolescents. This polymorphism may contribute to asthma susceptibility primarily under conditions of normal vitamin D levels (>20 ng/ml).
| S-EPMC4559891 | biostudies-literature
Project description:This study was designed to investigate the correlation of vitamin D receptor (VDR) gene polymorphism with bronchial asthma in children. Seventy patients admitted to Daqing Longnan Hospital and diagnosed as bronchial asthma for the first time from April 2015 to May 2017 were selected as observation group. Patients received routine treatment and intervention. Seventy healthy subjects admitted to hospital during the same period were enrolled as the control group. Vitamin D gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism assay; the levels of total serum immunoglobulin E (IgE) in the two groups were determined by electrochemiluminescence immunoassay; lung function levels in patients were measured using PowerCube (Germany) pulmonary function instrument before and after treatment, and the relationship between VDR gene polymorphism and lung function in children with bronchial asthma was analyzed. The difference in comparison of base frequency of rs1544410 locus of VDR gene had no statistical significance between the two groups (P>0.05). The locus CC frequency of rs7975232 of VDR gene in observation group was lower in the observation group than that in the control group (P<0.05); the locus AC and AA frequencies of rs7975232 of VDR gene were higher in the observation group than those in the control group (P<0.05). The level of vitamin D was lower in the observation group than that in the control group (P<0.05); the level of total serum IgE was higher in the observation group than that in the control group (P<0.05). The forced expiratory volume in 1 sec (FEV1), peak expiratory flow (PEF) and the ratio of FEV1 to forced vital capacity (FVC) in children with bronchial asthma in the observation group were higher after treatment than those before treatment (P<0.05). The correlation research displayed that VDR gene polymorphism was negatively correlated with lung function levels in children with bronchial asthma (P<0.05). The results showed that children with bronchial asthma are often accompanied by different degrees of changes in VDR gene polymorphism, which is negatively correlated with the severity of asthma, so vitamin D should be strengthened to ameliorate the prognosis of children.
| S-EPMC5795668 | biostudies-literature