25-Hydroxy Vitamin D, Vitamin D Receptor and Toll-like Receptor 2 Polymorphisms in Spinal Tuberculosis: A Case-Control Study.
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ABSTRACT:
SUBMITTER: Panwar A
PROVIDER: S-EPMC4998689 | biostudies-literature | 2016 Apr
REPOSITORIES: biostudies-literature
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25-Hydroxy Vitamin D, Vitamin D Receptor and Toll-like Receptor 2 Polymorphisms in Spinal Tuberculosis: A Case-Control Study.
Panwar Ajay A Garg Ravindra Kumar RK Malhotra Hardeep Singh HS Jain Amita A Singh Arvind Kumar AK Prakash Shantanu S Kumar Neeraj N Garg Rajiv R Mahdi Abbas Ali AA Verma Rajesh R Sharma Praveen Kumar PK
Medicine 20160401 17
Vitamin D deficiency and vitamin D receptor (VDR) gene abnormalities confer susceptibility to tuberculosis. Toll-like receptors (TLRs), such asTLR-2, are also important mediators of inflammatory response against Mycobacterium tuberculosis. We evaluated serum vitamin D, and VDR and TLR-2 gene polymorphisms in patients with spinal tuberculosis.This study comprised of 3 groups: spinal tuberculosis, pulmonary tuberculosis, and controls (each with 106 subjects). Enzyme-linked immunosorbent assay was ...[more]
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Project description:The relationship of four potentially functional polymorphisms of the vitamin D receptor (VDR) gene, ApaI, BsmI, FokI and TaqI , with tuberculosis susceptibility were considered. The aim of this meta-analysis was to explore the association between the four polymorphisms and tuberculosis risk in different ethnic backgrounds. Eligible case-control studies that were catalogued before April 1(st) 2013 were enrolled, and the heterogeneity between the studies was evaluated using a χ(2) based Q-test. Fixed and random effect models were built to evaluate the association of the four polymorphisms with the risk of tuberculosis, and the association between the four polymorphisms and tuberculosis was expressed as the odds ratio (OR) and 95% confidence interval (CI). Finally, twenty nine qualified studies were enrolled for this meta-analysis that included 6179 tuberculosis cases and 6585 healthy controls. The variant homozygote genotype of the FokI polymorphism was associated with a significantly increased risk of tuberculosis when compared to the heterozygote and wild type homozygote genotypes in the Chinese population (ff vs. Ff+FF: OR(recessive) =1.97, 95%CI: 1.32-2.93, P(bonferroni) =0.0032; heterogeneity test: χ(2)=0.24, P=0.62). For European subjects, the homozygote and heterozygote genotypes of the BsmI polymorphism were associated with a significantly decreased risk of tuberculosis when compared to the wild type homozygote (bb+Bb vs. BB: OR(dominant) =0.41, 95%CI, 0.22-0.76, P(bonferroni) =0.02; heterogeneity test: χ(2)=2.59, P=0.11). Based on the above results, we conclude that variants of the VDR gene that are homozygous for the FokI polymorphism might be more susceptible to tuberculosis in Chinese. Furthermore, larger sample studies are warranted to confirm the protective effects of BsmI variants on tuberculosis in the Europeans.
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Project description:Human genetic variants may affect tuberculosis susceptibility, but the immunologic correlates of the genetic variants identified are often unclear.We conducted a pilot case-control study to identify genetic variants associated with extrapulmonary tuberculosis in patients with previously characterized immune defects: low CD4+ lymphocytes and low unstimulated cytokine production. Two genetic association approaches were used: 1) variants previously associated with tuberculosis risk; 2) single nucleotide polymorphisms (SNPs) in candidate genes involved in tuberculosis pathogenesis. Single locus association tests and multifactor dimensionality reduction (MDR) assessed main effects and multi-locus interactions.There were 24 extrapulmonary tuberculosis cases (18 black), 24 pulmonary tuberculosis controls (19 black) and 57 PPD+ controls (49 black). In approach 1, 22 SNPs and 3 microsatellites were assessed. In single locus association tests, interleukin (IL)-1beta +3953 C/T was associated with extrapulmonary tuberculosis compared to PPD+ controls (P = 0.049). Among the sub-set of patients who were black, genotype frequencies of the vitamin D receptor (VDR) Fok1 A/G SNP were significantly different in extrapulmonary vs. pulmonary TB patients (P = 0.018). In MDR analysis, the toll-like receptor (TLR) 2 microsatellite had 76% prediction accuracy for extrapulmonary tuberculosis in blacks (P = 0.002). In approach 2, 613 SNPs in 26 genes were assessed. None were associated with extrapulmonary tuberculosis.In this pilot study among extrapulmonary tuberculosis patients with well-characterized immune defects, genetic variants in IL-1beta, VDR Fok1, and TLR2 were associated with an increased risk of extrapulmonary disease. Additional studies of the underlying mechanism of these genetic variants are warranted.
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Project description:AimTo evaluate the association between the FokI (rs2228570), ApaI (rs7975232), Bsml (rs1544410), TaqI (rs 731236), and Cdx2 (rs11568820) single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene and spontaneous preterm birth (SPTB), as well as their effect on clinical characteristics of women with SPTB and their newborns.MethodsThis case-control study enrolled women who gave birth at the Department of Obstetrics and Gynecology, University Medical Center Ljubljana between 2010 to 2019. Cases were 118 women with spontaneous initiation of PTB after natural conception and 119 controls with a term singleton delivery after an uncomplicated pregnancy. The molecular analysis of VDR SNPs employed polymerase chain reaction and restriction fragment length polymorphism.ResultsPatients and controls did not significantly differ in the distribution of genotype or allele SNP frequencies. However, the FokI polymorphism had a significant effect on newborn birth weight in women with SPTB but not in controls (F=5.17, P=0.007, one-way ANOVA with post-hoc Scheffe test), with newborns of FokI TT carriers having the lowest birth weight (P=0.011). No other VDR SNP was associated with any other clinical characteristic of women with SPTB and their newborns.ConclusionThe TT genotype of the VDR FokI polymorphism is associated with newborn birth weight in women of European origin with SPTB.
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Project description:BACKGROUND: The Toll-like receptor proteins are important in host defense and initiation of the innate and adaptive immune responses. A number of studies have identified associations between genetic variation in the Toll-like receptor genes and allergic disorders such as asthma and allergic rhinitis. The present study aim to search for genetic variation associated with allergic rhinitis in the Toll-like receptor genes. METHODS: A first association analysis genotyped 73 SNPs in 182 cases and 378 controls from a Swedish population. Based on these results an additional 24 SNPs were analyzed in one Swedish population with 352 cases and 709 controls and one Chinese population with 948 cases and 580 controls. RESULTS: The first association analysis identified 4 allergic rhinitis-associated SNPs in the TLR7-TLR8 gene region. Subsequent analysis of 24 SNPs from this region identified 7 and 5 significant SNPs from the Swedish and Chinese populations, respectively. The corresponding risk-associated haplotypes are significant after Bonferroni correction and are the most common haplotypes in both populations. The associations are primarily detected in females in the Swedish population, whereas it is seen in males in the Chinese population. Further independent support for the involvement of this region in allergic rhinitis was obtained from quantitative skin prick test data generated in both populations. CONCLUSIONS: Haplotypes in the TLR7-TLR8 gene region were associated with allergic rhinitis in one Swedish and one Chinese population. Since this region has earlier been associated with asthma and allergic rhinitis in a Danish linkage study this speaks strongly in favour of this region being truly involved in the development of this disease.
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Project description:Background: The association between vitamin D receptor (VDR) polymorphisms and the risk of asthma remains unclear. This study aimed to investigate the effect of VDR gene polymorphisms and VDR mRNA expression levels on respiratory function, nitric oxide levels in expiratory air, and serum vitamin D levels in children with asthma. Materials and Methods: The study included 80 healthy children (control group) and 100 asthmatic children (asthma group) between the age of 5 and 18 years. The VDR genotypes (ApaI, TaqI, and FokI) and VDR mRNA levels were determined in all groups. Results: There was no statistically significant difference in vitamin D levels between the asthma group and the control group (P?>?0.05). A significant association was found between both genotype (CC) of the TaqI polymorphism [odds ratio (OR)?=?0.2, 95% confidence interval (CI) (0.07-0.5), P?=?0.003] and genotype (CA) of ApaI polymorphisms [OR?=?0.2, 95% CI (0.07-0.8), P?=?0.02], and asthma risk. In addition, when single-nucleotide polymorphism allelic frequencies between asthma and control groups were compared there is no significant association (P?>?0.05). When compared to control group, VDR mRNA expression in asthma group decreased in genotypes CC and CA of ApaI and in genotypes TT and TC of TaqI (P?<?0.05). Conclusion: The results provide supporting evidence for an association between TaqI and ApaI polymorphisms and asthma susceptibility.
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Project description:We have carried out melanoma case-control comparisons for six vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) and serum 25-hydroxyvitamin D(3) levels in order to investigate the role of vitamin D in melanoma susceptibility. There was no significant evidence of an association between any VDR SNP and risk in 1028 population-ascertained cases and 402 controls from Leeds, UK. In a second Leeds case-control study (299 cases and 560 controls) the FokI T allele was associated with increased melanoma risk (odds ratio (OR) 1.42, 95% confidence interval (CI) 1.06-1.91, p=0.02). In a meta-analysis in conjunction with published data from other smaller data sets (total 3769 cases and 3636 controls), the FokI T allele was associated with increased melanoma risk (OR 1.19, 95% CI 1.05-1.35), and the BsmI A allele was associated with a reduced risk (OR 0.81, 95% CI 0.72-0.92), in each instance under a parsimonious dominant model. In the first Leeds case-control comparison cases were more likely to have a higher body mass index (BMI) than controls (p=0.007 for linear trend). There was no evidence of a case-control difference in serum 25-hydroxyvitamin D(3) levels. In 1043 incident cases from the first Leeds case-control study, a single estimation of serum 25-hydroxyvitamin D(3) level taken at recruitment was inversely correlated with Breslow thickness (p=0.03 for linear trend). These data provide evidence to support the view that vitamin D and VDR may have a small but potentially important role in melanoma susceptibility, and putatively a greater role in disease progression.
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Project description:BackgroundAssociation of Vitamin D receptor (VDR) polymorphisms with lumbar disc herniation (LDH) have been identified in several ethnic groups globally. Despite abundant sunlight, vitamin D deficiency is reported in many tropical countries. As vitamin D is a key modulator for intestinal calcium absorption, low vitamin D could contribute to low serum calcium leading to abnormalities of skeletal homeostasis. Therefore, present study was aimed to study the association of serum 25-hydroxyvitamin D (25(OH)D), serum calcium and VDR polymorphisms in a selected Sri Lankan population.Materials & methodsA case control study was conducted in 119 participants (cases = 51: controls = 68). Serum 25(OH)D levels were measured using ELISA. The VDR polymorphisms (Fok I and Taq I) were detected by polymerase chain reaction followed by restriction fragment length polymorphism.ResultsFindings indicated a significantly low (p = 0.000) 25(OH)D levels in cases (18.7±3.7 ng/mL) compared to controls(25.5±9.8 ng/mL) while 25(OH)D in both groups were below the reference range. Mean serum calcium levels in both groups were within normal reference range and was not significantly different among groups. Statistically significant association was not observed between VDR Fok I polymorphisms among cases and controls. Although Fok I polymorphism genotypes were in Hardy-Weinberg equilibrium (HWE), Taq I genotypes in controls violated HWE.ConclusionPresent study confirms that insufficient serum 25(OH)D levels in cases have major contribution to LDH. VDR Fok I polymorphisms did not have any significant association with LDH in Sri Lankan ethnicity.
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Project description:PurposeInnate immunity appears to play a key role in age-related macular degeneration (AMD). Although two previous studies reported that gene variations in Toll-like receptor (TLR)-3 and -4 are associated with AMD, other studies have not confirmed these associations. In this study, three independent samples (two U.S. clinic-based case-control study samples and one Australian population-based study sample) were used to further assess the association of the polymorphisms rs3775291 in TLR3 and rs4986790 in TLR4 with AMD.MethodsAMD cases and unrelated controls were collected from the National Eye Institute Clinical Center (NEI, n = 320), the Age-Related Eye Disease Study (AREDS, n = 483), and the Blue Mountains Eye Study (BMES, n = 852). DNA extracted from subjects was genotyped for rs3775291 and rs4986790, and the associations with AMD were investigated.ResultsNeither of the two polymorphisms rs3775291 and rs4986790 had a statistically significant association with AMD in any of the three sample sets or in combinations of the sets. Analysis of the combined geographic atrophy or neovascular AMD cases in the NEI, AREDS, and BMES sample sets also failed to demonstrate statistically significant associations of those two single nucleotide polymorphisms with advanced AMD.ConclusionsEven with previously verified samples sets and adequate study powers, the results did not confirm the reported associations of TLR3 rs3775291 and TLR4 rs4986790 with AMD in the three independent samples, individually or combined.
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Project description:Epidemiological studies regarding the relationship between vitamin D, genetic polymorphisms in the vitamin D metabolism, cigarette smoke and non-small cell lung cancer (NSCLC) risk have not been investigated comprehensively. To search for additional evidence, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and radioimmunoassay method were utilized to evaluate 5 single-nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR), 6 SNPs in 24-hydroxylase (CYP24A1), 2 SNPs in 1α-hydroxylase (CYP27B1) and 2 SNPs in vitamin D-binding protein (group-specific component, GC) and plasma vitamin D levels in 426 NSCLC cases and 445 controls from China. Exposure to cigarette smoke was ascertained through questionnaire information. Multivariable linear regressions and mixed effects models were used in statistical analysis. The results showed that Reference SNP rs6068816 in CYP24A1, rs1544410 and rs731236 in VDR and rs7041 in GC were statistically significant in relation to reduction in NSCLC risk (p < 0.001-0.05). No significant connection was seen between NSCLC risk and overall plasma 25-hydroxyvitamin D [25(OH)D] concentrations, regardless of smoking status. However, the mutation genotype of CYP24A1 rs6068816 and VDR rs1544410 were also significantly associated with increased 25(OH)D levels only in both the smoker and non-smoker cases (p < 0.01-0.05). Meanwhile, smokers and non-smokers with mutated homozygous rs2181874 in CYP24A1 had significantly increased NSCLC risk (odds ratio (OR) = 2.14, 95% confidence interval (CI) 1.47-3.43; p = 0.031; OR = 3.57, 95% CI 2.66-4.74; p = 0.019, respectively). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41-2.76; p = 0.015). However, smokers with mutated homozygous rs6068816 in CYP24A1 had significantly decreased NSCLC risk (OR = 0.43, 95% CI 0.27-1.02; p = 0.006); and smokers and non-smokers with mutated homozygous rs1544410 in VDR had significantly decreased NSCLC risk (OR = 0.51, 95% CI 0.34-1.17; p = 0.002; OR = 0.26, 95% CI 0.20-0.69; p = 0.001, respectively). There are significant joint effects between smoking and CYP24A1 rs2181874, CYP24A1 rs6068816, VDR rs10735810, and VDR rs1544410 (p < 0.01-0.05). Smokers with mutated homozygous rs10735810 in VDR had significantly increased NSCLC risk (OR = 1.93, 95% CI 1.41-2.76; p = 0.015). In summary, the results suggested that the lower the distribution of vitamin D concentration, the more the genetic variations in CYP24A1, VDR and GC genes may be associated with NSCLC risk. In addition, there are significant joint associations of cigarette smoking and vitamin D deficiency on NSCLC risk.
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