TaqI Rs731236 Research Articles

Vitamin D receptor gene polymorphisms and susceptibility to urolithiasis: a meta-regression and meta-analysis

BackgroundThe currently available data with respect to the association between vitamin D receptor (VDR) gene polymorphism and risk to urolithiasis are inconclusive and inconsistent. Hence, an exhaustive meta-analysis can solve the discrepancies and provide a hint for upcoming investigations. Herein, a meta-analysis was carried out to attain a conclusive estimate of the association between VDR gene single nucleotide polymorphisms (SNPs) and urolithiasis risk.MethodsThe major databases, including ISI Web of science, Scopus, and PubMed/MEDLINE were searched systematically from until June 2020 to retrieve all relevant studies. Association between VDR gene polymorphisms, including FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232), and urolithiasis risk was evaluated using pooled odds ratio (OR) and their corresponding 95% confidence interval (CI). Additionally, to seek for the potential source of heterogeneity, meta-regression analyses were exerted.ResultsLiterature search led to finally finding of 33 studies evaluating the VDR gene SNPs and urolithiasis risk. It was observed that none of the four SNPs were significantly associated with urolithiasis predisposition. However, subgroup analysis confirmed higher risk of urolithiasis in East-Asian and Caucasian population with ApaI and TaqI gene polymorphism. The analyses of sensitivity acknowledged the results stability.ConclusionAlthough this meta-analysis did not support the association of FokI, TaqI, BsmI, and ApaI in the overall polled analysis, it suggests that ApaI and TaqI SNPs is associated with increased risk of urolithiasis in East-Asian and Caucasians populations.

Study of The Polymorphism BsmI and TaqI in Vitamin D Receptor Gene in Egyptian Patients With Chronic Kidney Disease

Abstract Background Chronic kidney disease (CKD) is a major public health problem and a leading cause of morbidity and mortality worldwide. Chronic kidney disease mineral and bone disorders (CKD-MBD) is a common complication of CKD and an important cause of morbidity and decreased quality of life. Serum levels of 25-hydroxy vitamin D and parathyroid hormone (PTH) provide an accurate picture of bone turnover and mineralization states therefore they could be used with other serum bone biomarkers as non-invasive sensitive bone markers to help management of MBD in CKD. Due to the complex role played by vitamin D in kidney disease, the genotyping for vitamin D receptor (VDR) variants in CKD patients has been regarded as a way for improving the management of the disease. Objective The aim of the present work was to study the association of vitamin D receptor gene polymorphisms BsmI and TaqI with the chronic kidney disease and to assess its relationship with development and progression of chronic kidney disease-mineral bone disease. Subjects and Methods The study was conducted on 60 CKD-MBD patients in addition to 30 age- and sex- matched subjects serving as a healthy control group. Patients were subdivided into two subgroups according to the stage of CKD: subgroup 1a; 30 patients with CKD-MBD under conservative management (stages: 3 and 4 CKD) and subgroup 1b; 30 CKD-MBD patients with end-stage CKD on regular hemodialysis. Determination of BsmI (rs1544410, A>G) and TaqI (rs731236, C>T) polymorphisms of VDR gene was carried out using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Results The result of the present study revealed that VDR BsmI (rs1544410) gene polymorphism and alleles (Bb, bb) were not associated with susceptibility to the CKD or development and progression of CKD-MBD in the studied CKD-MBD patients. However, having the gene variants of VDR TaqI (rs731236) tt homotypic genotype increased the susceptibility to CKD-MBD compared to having the gene variant TT wild genotype and Tt heterotypic genotype. Moreover, VDR polymorphisms were associated with the mineral status in CKD-MBD Egyptian patients. The VDR BsmI wild (BB) genotypes and the VDR TaqI homotypic (tt) variant were found to be associated with development of severe secondary hyperparathyroidism, hypocalcemia and vitamin D deficiency in the studied Egyptian patients with CKD-MBD. Conclusion VDR BsmI gene polymorphism failed to prove any association with susceptibility to the CKD or development and progression of CKD-MBD. However, VDR TaqI tt homotypic genotype increased the susceptibility to CKD-MBD and progression toward severe secondary hyperparathyroidism, hypocalcemia and vitamin D deficiency.

Lipids profile in vitamin D insufficient/deficient subjects with different genotypes of vitamin D receptor gene

Background. Recent studies have demonstrated possible association between vitamin D deficiency and atherogenic dyslipidemia. However, there are practically no results from Russian investigations in this field. Objective. To assess serum lipids in women carrying various vitamin D receptor (VDR) gene variants. Design and methods . The study included 697 women aged between 35 to 55 years (mean age 43,4 ± 0,3 years). Anthropometric data including height, waist circumference, body mass index were measured. Serum lipid profile, 25-hydroxyvitamin D (25(OH)D) level and four VDR gene polymorphisms BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and FokI (rs2228570) were evaluated. The results showed high prevalence of abdominal obesity, dyslipidemia, vitamin D insufficiency/deficiency in the study group and 2,6 increased risk of high-density lipoprotein (HDL) cholesterol reduction in women with vitamin D deficiency. There were no differences in serum 25(OH)D between VDR genotypes. GG (BB) genotype carriers of BsmI (rs1544410) demonstrated higher triglyceride levels than subjects with GA, AA (Bb, bb) genotypes. Women with TT (AA) и TG (Aa) genotypes of ApaI (rs7975232) had higher total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared to GG (aa) genotype carriers. Conclusions. The study revealed the associations between low vitamin D status and decreased HDL cholesterol as well as between BsmI (rs1544410) and ApaI (rs7975232) VDR genotypes and atherogenic dyslipidemia.

Association of VDR (rs2228570, rs731236, rs7975232, rs1544410) and DBP (rs7041) genes polymorphisms with chronicity of hepatitis B in Iranian patients

BackgroundHost genetic factors and single nucleotide polymorphism (SNP) in host genes play important roles in the progression of disease stages and response to treatment of viral infections, including hepatitis B infection. Vitamin D plays a key role in a wide range of biological activities such as the immune response, proliferation and cellular differentiation. Since the biological effects of this vitamin are affected by the Vitamin D receptor (VDR) and the vitamin D-Binding Protein (DBP), in this study we investigated the association between VDR and DBP SNPs with the risk of chronic hepatitis B (CHB) infection in Iranian patients. MethodsOur case-control study consisted of two groups including 100 patients with CHB and 100 healthy controls. SNP of ApaI (rs7975232), TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570) VDR-related and DBP (rs7041) gene loci were determined by PCR-RFLP method. Serum ALT and AST levels and HBV virus load were determined and its association with SNP was investigated. Statistical analysis was performed using SPSS software (V22.0). ResultsThe results of this study showed that the TT (Homozygous Mutant) genotype of FokI locus (C>T; rs2228570) compared with CC (Homozygous Wild Type) and CT (Heterozygous) genotypes may be associated with an increased risk of CHB infection (P; 0.012, OR 2.674 (1.233–5.800), 95% CI). The T allele was also significantly associated with CHB infection (P; 0.009, OR 1.687 (1.136–2.506), 95% CI) compared to the C allele FokI. In this study, no significant relationship was found between CHB infection and rs7975232, rs731236, rs1544410 and rs7041 polymorphisms (P > 0.05). Also, there was no significant relationship between serum ALT and AST levels and HBV Viral load in patients with rs2228570 polymorphism (P > 0.05). DiscussionAccording to the results, VDR FokI (rs2228570) polymorphism has an impact on the chance of chronicity of hepatitis B in Iranian patients.

Investigation of The Vitamin D Receptor (VDR) Gene Polymorphisms in Lumbar Disc Herniation in Turkish Patients

<strong>Objective</strong>: Lumbar disc herniation (LDH) is a common degenerative disease. It is still not clear if there is a possible association between the vitamin D pathway and the etiopathogenesis of the disease. In this study, we investigated certain VDR polymorphisms which are known to affect vitamin D levels in patients with lumbar disc herniation. <br> <strong>Material and Method</strong>: TaqI (rs731236) and Fok-I (rs2228570) polymorphisms were studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 72 LDH patients and 81 healthy controls. <br> <strong>Results</strong>: After evaluation of our results, the frequency of LDH patients who have VDR Taq-I Tt genotype was significantly higher than the controls and carriers of Taq-I Tt genotype and t allele who had an increased risk for lumbar disc hernia cases, respectively p=0.002, OR:1.688, 95%CI:1.206-2.360; p=0.006, OR:1.420, 95%CI:1.104-1.825. VDR Fok-I genotypes did not differ significantly between lumbar disc herniation and control cases. (p=0.079). But, Ff genotype and f allele carriers had a higher risk for lumbar disk hernia than those with other genotypes, respectively p=0.025, OR:1.594, 95%CI:1.052- 2.414; p=0.037, OR:1.514, 95%CI:1.019-2.250. <br> <strong>Conclusion</strong>: Our study contributes to the identification of genetic risk factors for specific subgroups of patients with LDH, and emphasizes the contribution of these biomarkers to the detailed clinical evaluation of patients with genetic biomarkers.

Obstrüktif Uyku Apne Sendromuna Sahip Türk Hastalarda Vitamin D Reseptör Polimorfizmlerinin İncelenmesi

Objective: Numerous studies investigating Vitamin D receptor (VDR) polymorphisms in different populations have been present in current literature. For this reason, we designed a study to investigate the role of three known common VDR genetic polymorphisms (Apa-I/rs7975232, Bsm-I/ rs1544410 and Taq-I/rs731236) in Turkish individuals affected by Obstructive sleep apnea syndrome (OSAS). Methods: The study was carried out on a total of 175 consecutive subjects, including 80 OSAS patients and 95 healthy participants. Single Nucleotide Polymorphism (SNP) Detection was performed with the iPLEX® Assay and the MassARRAY® System for detection of Apa-I (rs7975232), Bsm-I (rs1544410), and Taq-I (rs731236) polymorphisms. Results: Fifty-seven C alleles (71.3%) and 59 T alleles (73.8%) were detected in the group of 80 OSAS patients in terms of rs1544410 polymorphism. When the patient and control groups were evaluated statistically at allelic level, it was observed that the T allele increased the risk of disease and this increase was statistically significant (Odds Ratio (OR) = 1.549 [Confidence Interval (CI): 1.012-2.371], (p=0.043). However, there were no significant differences between other VDR polymorphisms (rs7975232 and rs731236) and OSAS clinical data (p=0.6 and p=0.9, respectively). Discussion: As a conclusion, no statistically significant relationship was found between all three VDR polymorphisms and OSAS patients' clinical features. Further studies should be performed by creating a large sampling group. Finally, population studies should be given importance considering the variability of polymorphism according to ethnic origin.

Association of vitamin D receptor TaqI and ApaI genetic polymorphisms with nephrolithiasis and end stage renal disease: a meta-analysis

BackgroundThe deficiency of vitamin D receptor (VDR) or its ligand, vitamin D3, is linked to the development of renal diseases. The TaqI (rs731236) and ApaI (rs7975232) polymorphisms of VDR gene are widely studied for their association with renal disease risk. However, studies have largely been ambiguous.MethodsMeta-analysis was carried out to clarify the association of TaqI (2777 cases and 3522 controls) and ApaI (2440 cases and 3279 controls) polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN) and end stage renal disease (ESRD).ResultsThe VDR TaqI C-allele under allele contrast was significantly associated with ESRD in both fixed effect and random effect models, and ApaI C-allele with ESRD only under fixed effect model. Cochrane Q-test showed no evidence of heterogeneity for TaqI polymorphism and a significant heterogeneity for Apa I polymorphism. No publication bias was observed for both the polymorphisms.ConclusionsThe present meta-analysis identifies TaqI and ApaI polymorphisms of VDR gene as risk factors for renal diseases.

Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis

BackgroundThe association between the Vitamin D Receptor (VDR) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several researches. However, the findings were inconsistent and inconclusive. Therefore, we set out a meta-analysis of all eligible published case-control studies to obtain an exact evaluation of the association between VDR gene polymorphisms and MS.MethodAll relevant studies reporting the association between the VDR gene FokI (rs2228570), or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms and susceptibility to MS published up to May, 2019 were identified by comprehensive systematic search in the electronic database of web of science, Scopus, and PubMed. After that, the strength of association between VDR gene polymorphisms and susceptibility to MS was evaluated by odds ratio (OR) and 95% confidence interval (CI).ResultsA total of 30 case–control studies were included in the meta-analysis. The overall results suggested a significant association between TaqI polymorphism and MS risk under heterozygote genetic model (OR = 1.27, 95%CI = 1.01–1.59, random effect). Moreover, the pooled results of subgroup analysis declined presence of significant association under all defined genetic model. In subgroup analysis, BsmI polymorphisms was associated with increased risk of MS under recessive model in Asian populations. On the other hand, ApaI polymorphism was associated with decreased risk of MS under recessive and aa vs. AA model in Asian populations.ConclusionThis meta-analysis suggested a significant association between TaqI polymorphism and MS susceptibility. Furthermore, BsmI polymorphism was associated with increased risk of MS in Asian populations. In contrast, ApaI polymorphism was associated with decreased risk of MS in Asian populations. Future large-scale studies on gene–environment and gene–gene interactions are required to estimate risk factors and assist early diagnosis of patients at high risk for MS.

VDR Gene Polymorphisms and Allergic Diseases: Evidence from a Meta-analysis

ABSTRACTAssociations between vitamin D receptor (VDR) gene polymorphisms and allergic diseases were already reported by many publications. The aim of this meta-analysis was to clarify associations between VDR gene polymorphisms and allergic diseases by combing the results of all relevant publications. Eligible publications were searched from Pubmed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies. Twenty-one studies were included in this study. Combined results proved that VDR rs1544410 BsmI (over-dominant comparison: p = .04, OR = 1.14, 95% CI 1.01–1.29; allele comparison: p = .03, OR = 1.11, 95% CI 1.01–1.22) and rs731236 TaqI (dominant comparison: p = .01, OR = 1.18, 95% CI 1.04–1.33) polymorphisms were both associated with allergic diseases. In subgroup analyses by type of disease, we confirmed positive results for rs1544410 BsmI polymorphism in both asthma and atopic dermatitis, and for rs731236 TaqI polymorphism in atopic dermatitis. Besides, in subgroup by ethnicity of participants, we observed significant associations with allergic diseases for rs7975232 ApaI polymorphism in Caucasians, for rs1544410 BsmI polymorphism in Asians and Caucasians, and for rs731236 TaqI polymorphism in Asians. We also investigated associations between VDR rs2228570 FokI polymorphism and allergic diseases, yet no any positive results were detected for this polymorphism. If we only focused on asthma, then positive findings were detected for rs1544410 BsmI polymorphism in Caucasians, and for rs731236 TaqI polymorphism in Asians. Collectively, this meta-analysis proved that VDR rs7975232 ApaI, rs1544410 BsmI and rs731236 TaqI gene polymorphisms may confer susceptibility to allergic diseases in certain populations.

Vitamin D plasma concentration and vitamin D receptor genetic variants confer risk of asthma: A comparison study of Taiwanese and Mongolian populations

BackgroundRecent 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. MethodsIn 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. ResultsWe 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. ConclusionOur 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.

Vitamin D receptor gene polymorphism and susceptibility to asthma: Meta-analysis based on 17 case-control studies

BackgroundDuring the last decade, several studies have evaluated the potential association between vitamin D receptor (VDR) gene polymorphism and susceptibility to asthma. In spite of valuable findings, the results are still contradictory. Therefore, a comprehensive meta-analysis not only solves discrepancies but provides a clue for future projects. ObjectiveThis meta-analysis was performed to identify whether VDR gene polymorphisms (FokI (rs2228570) or TaqI (rs731236) or BsmI (rs1544410) or ApaI (rs7975232)) play a role in the risk of asthma. MethodsElectronic search of Web of Science, Scopus, and PubMed databases were systematically conducted from their inception until June 2019, to identify all published studies. Eligibility of the studies was confirmed by precise inclusion and exclusion criteria, and the resultant studies were analyzed. ResultsA total of 17 studies concerning VDR gene polymorphisms and asthma risk were included in this meta-analysis. The results of pooled analysis indicated a statistically significant association between FokI SNP (dominant model [OR = 0.78, 95% CI, 0.62-0.98, random effect model] and allelic model [OR = 0.81, 95% CI, 0.67-0.98, random effect model]) and TaqI SNP (homozygote contract model [OR = 0.70, 95% CI, 0.54-0.89]) with asthma risk. Moreover, subgroup analysis showed that ethnicity influences asthma risk in Asian, African, and American populations. The sensitivity analyses confirmed the stability of the results. ConclusionThis meta-analysis suggests that VDR gene polymorphism is associated with the risk of asthma.

Vitamin D receptor ApaI (rs7975232), BsmI (rs1544410), Fok1 (rs2228570), and TaqI (rs731236) gene polymorphisms and susceptibility to pulmonary tuberculosis in an Iranian population: A systematic review and meta-analysis

Polymorphisms of vitamin D receptors (VDRs), ApaI, BsmI, FokI, and TaqI might affect susceptibility to tuberculosis (TB). In this systematic review and meta-analysis, all published articles which investigated the effects of these polymorphisms on the risk of TB in the Iranian population were retrieved. PubMed and Scopus were searched with no date or language restrictions. In this meta-analysis, the Comprehensive Meta-Analysis (CMA) version 2.0 and random effects model were applied. The association of polymorphisms with TB risk was assessed by measuring the odds ratio (ORs) at 95% CI. Heterogeneity was investigated based on Cochran Q-test and I2-index statistics. The significance level was set at 0.05. Also, Egger's regression intercept was determined to measure publication bias. A total of six articles on Iranian populations were included. TaqI (5/6 included studies) showed a significant association with the increased risk of TB based on ORs (allele comparison: 1.57 (1.0, 2.3), p-value: 0.02; additive model of tt/TT: 1.57 (0.9, 2.5), p-value: 0.05; recessive model (tt/Tt+TT): 1.99 (1.2, 3.2), p-value: 0.00; dominant model (tt+Tt/TT): 1.98 (1.1, 3.5), p-value: 0.01). BsmI showed a significant positive effect on TB risk only in its dominant genotype (bb+bB/BB) (1.44 (1.0, 1.9); p-value: 0.02). FokI and ApaI did not show any significant effects on TB development in Iranian populations. Findings showed the significant effect of TaqI polymorphism in all genetic models and the dominant model of BsmI on the increased risk of TB. However, the effects of TaqI and BsmI should be further investigated in a larger sample size.

Impact of vitamin D and vitamin D receptor TaqI polymorphism in primary human myoblasts.

The CC genotype of the vitamin D receptor (VDR) polymorphism TaqI rs731236 has previously been associated with a higher risk of developing myopathy compared to TT carriers. However, the mechanistic role of this polymorphism in skeletal muscle is not well defined. The effects of vitamin D on patients genotyped for the VDR polymorphism TaqI rs731236, comparing CC and TT carriers were evaluated. Primary human myoblasts isolated from 4 CC carriers were compared with myoblasts isolated from four TT carriers and treated with vitamin D in vitro. A dose-dependent inhibitory effect on myoblast proliferation and differentiation was observed concurrent with modifications of key myogenic regulatory factors. RNA sequencing revealed a vitamin D dose–response gene signature enriched with a higher number of VDR-responsive elements (VDREs) per gene. Interestingly, the greater the expression of muscle differentiation markers in myoblasts, the more pronounced was the vitamin D-mediated response to suppress genes associated with myogenic fusion and myotube formation. This novel finding provides a mechanistic explanation to the inconsistency regarding previous reports of the role of vitamin D in myoblast differentiation. No effects in myoblast proliferation, differentiation or gene expression were related to CC vs TT carriers. Our findings suggest that the VDR polymorphism TaqI rs731236 comparing CC vs TT carriers did not influence the effects of vitamin D on primary human myoblasts and that vitamin D inhibits myoblast proliferation and differentiation through key regulators of cell cycle progression. Future studies need to employ strategies to identify the primary responses of vitamin D that drive the cellular response towards quiescence.

Association of vitamin D receptor polymorphisms and nephrolithiasis: A meta-analysis

Nephrolithiasis is a complex disease in which its pathophysiology is strongly influenced by genetics. Polymorphisms of the vitamin D receptor (VDR) gene have been reported to be associated with the development of kidney stones which in most cases are composed predominantly of calcium salts. For the purpose of this study, we performed a systematic review and meta-analysis to analyze the association of BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms with nephrolithiasis. A systematic search was performed up to June 2018 using PubMed, Embase and ISI Web of Knowledge databases. The keywords used for the search were “vitamin D receptor or VDR” and “polymorphisms or SNPs” combined with “urolithiasis or nephrolithiasis”. A meta-analysis was performed with the results of the selected and included studies. After analyzing 23 publications, we observed that BsmI polymorphism (rs1544410) has a protective association against nephrolithiasis (Allelic model: OR = 0.84, CI 95% 0.73–0.96, Z p-value 0.015; homozygous model: OR = 0.72, CI 95% 0.54–0.97, Z p-value 0.033). Furthermore, we observed that FokI polymorphism (rs2228570) has a decreased risk of nephrolithiasis in the heterozygous model in the presence of heterogeneity (OR = 0.69, CI 95% 0.48–0.99, Z p-value 0.044), as well as in the absence of heterogeneity (OR = 0.81, CI 95% 0.66–0.99, Z p-value 0.045). Additionally, TaqI polymorphism (rs731236) was associated with a decreased risk of nephrolithiasis in the heterozygous model (OR = 0.77, CI 95% 0.63–0.94, Z p-value 0.010), and no overall association was observed with ApaI polymorphism (rs7975232). This meta-analysis provided comprehensive evidence that VDR polymorphisms are associated with upper urinary tract stones incidence and the genetic variants we studied provide protection against nephrolithiasis.

Vitamin D Receptor gene polymorphisms and plasma levels are associated with lumbar disc degeneration

The purpose of this study was to investigate the association of Vitamin D Receptor (VDR) gene polymorphisms and VDR levels with lumbar disc degeneration (LDD). TaqMan SNP Genotyping Assay was utilized to probe VDR gene polymorphisms including the FokI (rs2228570), ApaI (rs7975232) and TaqI (rs731236) in 454 patients with LDD and 485 controls. Enzyme-Linked Immunosorbent Assay (ELISA) was used to detect plasma VDR levels. The patients with LDD were divided into three subgroups (subgroup 1: lumbar disc herniation; subgroup 2: lumbar spinal stenosis; subgroup 3: lumbar spondylolisthesis) to further probe the association of plasma VDR levels and VDR gene polymorphisms and LDD. Moreover, immunohistochemistry (IHC) was implemented to evaluate VDR expression in lumbar degenerated disc and normal disc. Allele and genotype frequency of TaqI (rs731236) were significantly different in patients with LDD and controls (all P < 0.05). For TaqI polymorphism, the frequencies of T allele were significantly higher in the LDD patients compared with controls (OR = 1.319; 95%CI 1.091 to 1.595; P = 0.004, adjusted (OR = 1.319; 95%CI 1.091 to 1.595; P = 0.004, adjusted OR = 1.383; 95%CI 1.135 to 1.684; P = 0.016). Furthermore, the allele distribution showed a higher frequency of the T allele in the patients with lumbar disc herniation in subgroup 1 (OR = 1.384; 95% CI 1.105 to 1.732; P = 0.004, adjusted OR = 1.319; 95%CI 1.091 to 1.595; P = 0.016). Plasma VDR levels and VDR expression were significantly lower in patients with LDD compared with controls (all P < 0.05). Moreover, the TT genotype of TaqI polymorphism was significantly associated with lower plasma VDR levels in patients with LDD (P = 0.002). TaqI (rs731236) polymorphism was associated with a predisposition to LDD. Plasma VDR and VDR expression levels may be the marker for the occurrence and development of LDD.

Lower Vitamin D Levels, but Not VDR Polymorphisms, Influence Type 2 Diabetes Mellitus in Brazilian Population Independently of Obesity.

Background and Objectives: Vitamin D levels have been associated with a diversity of diseases, including obesity. Vitamin D presents a pleiotropic action, and can regulate insulin secretion and inflammatory responses. Vitamin D receptor (VDR) gene polymorphisms are involved in the gene expression regulation and have been associated with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between the polymorphisms ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810), and TaqI (rs731236) in the VDR gene in people diagnosed with T2DM, and plasma 25-hydroxivitamin D levels [25(OH)D]. Materials and Methods: A total of 101 T2DM patients and 62 gender, age, and body mass index (BMI) matched non-diabetic controls were included in this study. Molecular analyzes were performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). The plasma 25(OH)D levels were measured by high performance liquid chromatography. Results: The plasma 25(OH)D levels were lower in T2DM patients (17.2 (16.6) ng/mL) when compared with the control subjects (30.8 (16.2) ng/mL, p < 0.0001), independently of obesity status. We found no difference between genotypic and allelic frequencies of the VDR polymorphisms when comparing the T2DM group and control group (p > 0.05 for all), and did not show any association with plasma 25(OH)D levels. Conclusions: These results suggest that T2DM is associated with lower plasma 25(OH)D levels, which are not related to BMI and VDR gene polymorphisms.

The VDR gene FokI polymorphism is associated with gestational diabetes mellitus in Turkish women

BackgroundThe association between the vitamin D receptor (VDR) gene and gestational diabetes mellitus (GDM) has not been investigated in Turkish pregnant women. We aimed to investigate associations between VDR gene BsmI (rs15444410), ApaI (rs7975232), FokI (rs19735810), and TaqI (rs731236) single nucleotide polymorphisms (SNPs) and GDM.Material-methodsThis case-control study comprised 100 women with GDM and 135 pregnant women without GDM. The VDR polymorphism was evaluated using Sanger-based DNA sequencing.ResultVDR gene ApaI, BsmI, and TaqI SNPs did not differ between women with and without GDM (each, p > 0.05). ApaI, BsmI, and TaqI were not associated with GDM risk. The VDR gene FokI CT/TT genotype was associated with an increased GDM risk (CT vs. CC, OR = 1.84, 95% CI: [1.05–3.23], p = 0.031; TT vs. CC, OR = 3.95, 95% CI: [1.56–9.96], p = 0.002; CT/TT vs. CC, OR = 2.29, 95% CI: [1.35–3.89], p = 0.002; and CT/CC vs. TT, OR = 3.02, 95% CI: [1.23–7.38], p = 0.012). The FokI-TT genotype was more associated with younger age and higher glucose, HbA1c, and HOMA-IR than the CC and CT genotype. FokI-T was positively correlated with log-HOMA-IR (r = 0.326, p = 0.004). FokI SNPs were independently associated with GDM after adjusting for BMI and age (β = 1.63, 95% CI: [1. 2-4.2], p = 0.012). There were no associations between the FokI, ApaI, BsmI and TaqI haplotypes and GDM.ConclusionVDR gene FokI SNPs were independently associated with having GDM in Turkish women. VDR gene FokI SNPs might contribute to insulin resistance of developing GDM.

Vitamin D receptor rs7975232, rs731236 and rs1544410 single nucleotide polymorphisms, and 25-hydroxyvitamin D levels in Egyptian children with type 1 diabetes mellitus: effect of vitamin D co-therapy.

Purpose: We aimed to examine the possible association role of vitamin D and vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) in type 1 diabetes mellitus (T1DM) development, glycemic control and complications among a cohort of Egyptian children.Subjects and methods: A prospective case-control study has been conducted on 50 Egyptian children with T1DM who were comparable with 50 controls. Vitamin D and HbA1c were measured. VDR-SNPs [ApaI (rs7975232), TaqI (rs731236) and BsmI (rs1544410)] detection was done by polymerase chain reaction through restriction fragment length polymorphism (PCR-RFLP) technique. Vitamin D supplements were given to the included T1DM children with low vitamin D and reassessments of both HbA1c% and 25(OH)D serum levels were performed in those children three months later.Results: Eighty percent of the included diabetic patients have poor glycemic control. Vitamin D was deficient in 68% and insufficient in 16% of diabetic patients. Significant improvements in both vitamin D and glycemic status among T1DM children, who have low vitamin D and received vitamin D supplementations. There were significantly negative correlations between serum levels of vitamin D with both HbA1c % (r= –0.358, P˂0.05) and daily insulin dose (r=−0.473, P˂0.05). Compared with controls, T1DM children presented more commonly with ApaI a allele (OR: 2.87; 95%CI: 1.39–5.91, P˂0.05) and BsmI b allele (OR: 4.38; 95%CI: 2.30–8.33, P˂0.05). TaqI t allele wasn’t significantly differing among patients and controls (P˃0.05). Aa+aa and Bb+bb genotypes were significantly higher among T1DM vs the controls (OR: 3.08;, 95%CI: 1.33–7.15, P˂0.05 and OR: 9.33; 95%CI: 3.61–24.17, P˂0.05respectively).Conclusion: ApaI and BsmI were associated with risk of T1DM development among Egyptian children. Low vitamin D status was frequently occurring among T1DM with significant improvement in the glycemic control of such children when adding vitamin D supplements to the standard insulin therapy.

The Association of Vitamin D Receptor Gene Polymorphism with Lung Cancer Risk: An Update Meta-analysis.

The association between vitamin D receptor (VDR) genetic polymorphism and lung cancer risk has been evaluated by the previous meta-analyses. Due to the emergence of novel studies and inappropriate inclusion of overlapping populations, an updated meta-analysis on recent evidences is necessarily needed. We comprehensively searched databases of PubMed, Web of Science and Chinese National Knowledge Infrastructure and finally obtained 7 eligible studies according to the inclusion criteria. Four positions on VDR gene, namely ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810) and TaqI (rs731236), were considered in this investigation. Data pooling found no significant association of lung cancer risk with ApaI or FokI. In contrast, it was indicated that the BsmI A allele was negatively related to the lung cancer risk, compared with the G allele (OR = 0.51, 95% CI = 0.33-0.79). Individuals with BsmI AA (OR = 0.53, 95% CI = 0.26-1.11) and AG genotypes (OR = 0.46, 95% CI = 0.30-0.71) showed decreased risk of lung cancer, compared with those of GG genotype. Regarding the TaqI polymorphism, the T allele carriers were at increased risk of lung cancer (OR = 1.25, 95% CI = 1.04-1.50). Compared with the TaqI TC+CC genotype, the TT genotype was positively associated with lung cancer risk (OR = 1.42, 95% CI = 1.11-1.82). No publication bias was identified in any of the analysis. In conclusion, VDR genetic polymorphism may be correlated to lung cancer risk. Given limited number of the included studies, more observations are warranted to draw a safer conclusion.

Association of vitamin D receptor gene variants with polycystic ovary syndrome: a meta-analysis

BackgroundPolycystic 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.MethodsEnglish 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.ResultsTotally, 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.ConclusionsOur 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.