Vitamin D receptor gene polymorphisms role in COVID-19 severity: Results of a Mexican patients' cohort.

Vitamin D status has been involved with coronavirus disease 19 (COVID-19) severity. This may be mediated by vitamin D metabolism regulatory genes. Of interest is the vitamin D receptor (VDR) gene, which has been previously associated with other inflammatory and respiratory diseases. In order to investigate the role of VDR gene polymorphisms in COVID-19 severity and outcome, a total of 292 COVID-19 patients were classified according to severity in moderate (n = 56), severe (n = 89) and critical (n = 147) and, according to outcome in survivor (n = 163) and deceased (n = 129), and analysed for FokI and TaqI VDR gene polymorphisms by polymerase chain reaction-based restriction enzyme digestion. The FokI and TaqI single nucleotide polymorphisms (SNPs) were not associated with COVID-19 severity or mortality individually but when analysed by haplotype, TC was associated with an increased risk of presenting critical COVID-19. Additionally, FokI CT genotype was more frequent in COVID-19 patients with hypertension, and T allele carriers presented higher aspartate aminotransferase levels. Our results suggest a relationship between VDR FokI and TaqI SNPs and COVID-19 severity in Mexican population. Although there are some previous reports of VDR polymorphisms in COVID-19, this represents the first report in Latin American population. Further studies on other populations are encouraged.

Molecular investigation of vitamin D receptor (VDR) genetic variants and their impact on VDR mRNA and serum vitamin D levels in allergic rhinitis in an Indian population: A case-control study.

Vitamin D deficiency is widespread and poses a significant health concern, as emerging research links it to allergic diseases owing to its immunomodulatory functions. The optimal functioning of vitamin D and its activation depend on its nuclear receptor, vitamin D receptor (VDR). Genetic variants of VDR have been explored as potential factors in autoimmune and allergic diseases, with limited studies on their association with allergic rhinitis (AR). The present investigation aims to analyse the role of three VDR genetic variants - TaqI, FokI and BsmI - in AR susceptibility and their impact on VDR mRNA and serum vitamin D levels. A total of 550 subjects, consisting of 250 AR cases and 300 age- and gender-matched controls, underwent genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). VDR mRNA and vitamin D levels were determined by quantitative real-time PCR and chemiluminescence, respectively. Although TaqI did not exhibit significant differences, FokI demonstrated a noteworthy association with AR, particularly with the CC genotype (odds ratio [OR]: 3.34; confidence interval [CI]: 1.79-6.23). Similarly, BsmI revealed an increased risk for AR, with the GA + AA genotypes showing a 2.2-fold elevated risk (OR: 2.20; CI: 1.53-3.16). VDR mRNA expression was threefold lower in AR patients (p < .0001), accompanied by reduced serum vitamin D levels (p < .0001). In addition, CC (p = .01) and AA (p = .02) genotypes of FokI and BsmI were associated with reduced VDR mRNA levels, whereas TaqI showed no such association. Similarly, heterozygous genotypes of TaqI and FokI, as well as homozygous AA of BsmI, correlated with lower serum vitamin D levels (p < .001). This study emphasizes the intricate relationship among VDR genetic variations, altered VDR activity, immune modulation and vitamin D metabolism in AR. Further research involving diverse populations is crucial for confirming and generalizing these findings, paving the way for personalized therapeutic interventions in vitamin D-related disorders.

Genetic Diversity in Bronchial Asthma Susceptibility: Exploring the Role of Vitamin D Receptor Gene Polymorphisms in Varied Geographic Contexts.

Bronchial asthma (BA) exhibits varying prevalence across global populations, prompting a comprehensive investigation into genetic and environmental determinants. Vitamin D is a potent immunomodulator capable of suppressing inflammatory signals in several cell types involved in the asthmatic response; it exerts effects on the immune system by binding to the nuclear vitamin D receptor (VDR). VDR gene genetic variations are affecting serum vitamin D levels with a possible role in the BA risk. The current study aimed to examine the complex interaction of various factors (genetic background, serum vitamin D levels, and geographic location) to identify differences in the influence of these factors on the susceptibility to asthma between populations at different latitudes. Focusing on Eastern European cohorts from Latvia and Lithuania and comparing them with published data on East Asian populations, we explore the impact of VDR gene polymorphisms on BA susceptibility. Genotyping four key VDR SNPs and assessing their association with 25-hydroxyvitamin D levels, our study unveils significant associations of the studied loci with the risk of asthma-both risk-reducing and increasing effects, differently distributed between Baltic and East Asian populations. The functional effects of in silico VDR gene genetic variations are also identified and discussed.

Genetic susceptibility of vitamin D receptor gene polymorphisms on autosomal recessive primary microcephaly patients in Pakistani population: a case-control and in-silico study.

BACKGROUND: Autosomal recessive primary microcephaly (MCPH) is a rare genetic disorder that leads to reduced cerebral cortex caused by a mutation in corticogenesis. The expression of the Vitamin D receptor (VDR) gene is involved in the proliferation and differentiation of neural stem cells, and VDR polymorphisms have been associated with various neurological disorders. However, their relationship with MCPH has not been explored. This study aimed to investigate the association of VDR polymorphisms with MCPH due to its role in Wnt signaling pathway and its In-silico analysis. METHODS: Blood samples of 64 MCPH patients and 52 controls were collected to genotype VDR SNPs (TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). In-silico tools were also used to assess the effects of exonic SNPs on mRNA and protein structure and pathogenicity of exonic and intronic SNPs. RESULTS: The study found that serum 25-OH vitamin D3 levels were significantly different in MCPH patients and healthy controls (P = 0.000). The genetic analysis showed that VDR polymorphisms of FokI and BsmI were seven times more frequent in MCPH patients than in controls (P < 0.05) and the recessive model for TaqI and dominant model for BsmI polymorphisms were also associated with the pathogenesis of MCPH. In-silico analysis showed that the pathogenicity effects of rs2228570 and rs1544410 are neutral while rs731236 causes a silent mutation which has no effect on VDR protein. CONCLUSION: VDR polymorphisms of FokI and BsmI are associated with the risk of MCPH. These findings suggest that VDR polymorphisms play a role in MCPH, which could provide important insights for understanding the molecular mechanisms of the disease.

Impact of vitamin D receptor gene polymorphisms (TaqI and BsmI) on the incidence and severity of coronary artery disease: a report from southern Iran.

BACKGROUND: The association of vitamin D level and vitamin D receptor (VDR) gene polymorphisms with the prevalence of coronary artery disease (CAD) has been evaluated in various studies; however, the reported results were inconsistent. Hence, we aimed to investigate the impact of two VDR gene polymorphisms, TaqI (rs731236) and BsmI (rs1544410), on the incidence and severity of CAD in Iranian population. METHODS: Blood samples were collected from 118 CAD patients underwent elective percutaneous coronary intervention (PCI) and 52 control subjects. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed for genotyping. SYTNAX score (SS) was calculated as a grading tool for complexity of CAD by an interventional cardiologist. RESULTS: TaqI polymorphism of VDR was not associated with the incidence of CAD. A significant difference was observed between CAD patients and controls regarding BsmI polymorphism of VDR (p < 0.001). GA and AA genotypes was significantly associated with a decreased risk of CAD (p = 0.01, p-adjusted = 0.01 and p < 0.001, p-adjusted = 0.001 respectively). A allele of BsmI polymorphism was shown to have a protective effect against CAD (p < 0.001, p-adjusted = 0.002). No association was found between TaqI and BsmI polymorphisms of VDR and SS as a measure of CAD severity. CONCLUSION: Association of BsmI genotypes with the incidence of CAD revealed that the genetic variation of VDR might play a role in the pathogenesis of CAD.

Increased susceptibility to complicated pneumonia among egyptian children with FokI (rs2228570), not TaqI (rs731236), vitamin D receptor gene polymorphism in association with vitamin D deficiency: a case-control study.

BACKGROUND: Determining a genetic contribution to the development of complicated community-acquired pneumonia in children may help understand underlying pathogenesis. We aimed to investigate the association between two vitamin D receptor (VDR) gene polymorphisms, FokI and TaqI, and susceptibility to complicated pneumonia in Egyptian children compared to uncomplicated pneumonia. Associations with 25 hydroxy-vitamin D serum level were studied. METHODS: This was a case-control study that included 320 participants divided into 2 groups: patients and controls. The patients' group included 100 children hospitalized with complicated pneumonia and 100 with uncomplicated pneumonia. 120 age and sex-matched apparently healthy children served as controls. The VDR FokI and TaqI polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. 25 hydroxy-vitamin D level was estimated in serum using ELISA. RESULTS: Regarding FokI, homozygous CC genotype was more common in complicated (52%) than uncomplicated pneumonia (28%) and controls (10%) (OR = 65; 95%CI (5.13-822.63), p < 0.001) and (OR = 4.3; 95%CI (0.7-27.16), p = 0.003), respectively. Children carrying C allele possessed 3 higher odds for complicated than uncomplicated pneumonia (OR = 3.08; 95%CI (1.33-7.14), p < 0.001). Heterozygous CT genotype increased susceptibility to complicated pneumonia (OR = 13.7; 95%CI (4.6-40.1), p < 0.001), not uncomplicated pneumonia (OR = 1.56; 95%CI (0.86-2.85), p = 0.145). Among complicated pneumonia, vitamin D level was lower in CC (6.92 ± 2.6ng/ml) than CT (9.55 ± 3.2 ng/ml) and TT genotype carriers (13.13 ± 3.6ng/ml) (p < 0.001). There was no significant difference between patients and controls as regards TaqI genotypes and alleles. CONCLUSION: In association with vitamin D deficiency, VDR gene FokI polymorphism, not TaqI, is a genetic risk factor for complicated pneumonia in Egyptian children.

Assessment of A1 and A2 variants in the CNS2 gene of some cattle breeds by using ACRS-PCR method.

The aim of this study is to reveal ß-casein polymorphism of some cattle breeds and also the potential to produce A2 milk from existing animals and to develop strategies in this area. Therefore, a total of 400 cattle, 100 animals from each breed of Holstein, Brown Swiss, Jersey and Simmental raised commonly in Turkey, were obtained, and C > A polymorphism in 67th amino acid in the 7th exons of ß-casein gene was determined by TaqI enzyme with PCR-ACRS method. Blood samples were collected from dairy cattle farms raising Holstein, Brown Swiss and Jersey breeds from Konya province and Simmental breed from Kütahya province in Turkey. A1 and A2 allele frequencies in Holstein, Brown Swiss, Jersey and Simmental cattle breeds were determined as 0.475/0.525, 0.370/0.630, 0.215/0.785 and 0.440/0.560, respectively. The highest A2 allele frequency (0.785) was found in Jersey breed. A1A1 genotypes in Holstein, Brown Swiss, Jersey and Simmental breeds were 0.240, 0.150, 0.030 and 0.160, respectively; A1A2 genotypes were 0.470, 0.440, 0.370 and 0.560, respectively; A2A2 genotypes were determined as 0.290, 0.410, 0.600 and 0.280, respectively. In these breeds, the highest A2A2 genotype frequency was found in Jersey (0.600), the lowest A1A1 genotype frequency (0.030) was found in Jersey and the highest A1A2 genotype frequency (0.560) was found in Simmental. Holstein, Brown Swiss, Simmental and Jersey populations were at the level of Hardy-Weinberg in terms of ß-casein gene (p > 0.05). The average Ho, He and PIC values were calculated as 0.460, 0.469 and 0.605, respectively. In conclusion, the frequency of commonly reared cattles in Turkey especially Brown Swiss, and Jersey breeds in A2A2 genotype are satisfactory, but it can be said that the use of animals with A2 allele in selection is extremely important for increasing A2 milk producing potential in the future.

TaqI polymorphism T/t genotypes at the vitamin D receptor gene (VDR) are associated with increased serum vitamin D levels in mild and moderate psoriasis vulgaris: A pilot study.

BACKGROUND: Several types of polymorphisms in vitamin D receptor (VDR) have been found in psoriasis. AIM: This study looked at the role of the TaqI polymorphism in the VDR gene as a factor in changing plasma 25-hydroxyvitamin D [25(OH)D] levels in psoriasis patients and to see if it had any relationship with disease severity. SUBJECTS AND METHODS: Clinical examination, serum 25(OH)D level measurement, molecular studies and TaqI genotyping by PCR and RFLP were performed for the two groups. RESULTS: The T/t genotypes of TaqI polymorphism genotypes were most common in patients, while the t/t genotypes were more abundant in healthy subjects. The T allele was high in the patient group in comparison with the normal subjects, but there were no significant differences (p = 0.421). Patients with T/t TaqI genotypes had higher levels of 25(OH)D than those with T/T and t/t (p = 0.004). Moderate psoriatic patients with the T/t genotype had relatively high 25(OH)D levels compared with moderate patients with the T/t and t/t genotypes (p = 0.001). CONCLUSION: The increase in 25(OH)D titers in moderate patients is greater than that in mild and severe patients. T/t genotypes are associated with increased 25(OH)D levels in moderate and mild patients.

Vitamin D receptor gene polymorphism TaqI (rs731236) and its association with the susceptibility to coronary artery disease among Pakistani population.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of mortality in Pakistan and also worldwide. Vitamin D receptor (VDR) regulates the transcription of many genes and has a significant impact on inflammation and the morphology of cardiac cells. Genetic variation in the VDR gene such as the TaqI polymorphism (rs731236) may have an impact that causes adverse effects. Accordingly, it is important to determine possible association of the TaqI polymorphism (rs731236) with CAD. METHODS: The study included blood samples from 1016 subjects: 516 from CAD patients and 500 from age- and gender-matched controls. Genomic DNA was extracted by standard salting out method. Targeted variation was amplified by an allele-specific polymerase chain reaction (PCR). PCR products were examined and genotyped on agarose gel electrophoresis represented by an amplified product size of 148 bp followed by Sanger sequencing to validate variations. RESULTS: Serum vitamin levels, as observed using enzyme-linked immunosorbent assay, were found to be insufficient in both CAD patients (20.52 ± 0.06 ng/ml) and controls (21.6981 ± 0.05 ng/ml). The TaqI polymorphism (rs731236) T>C was found to be significantly associated with CAD (p < 0.0001). The odds ratio showed that the risk increases by 1.8-fold with variant C allele. Dominant, co-dominant and over dominant genetic model analyses suggested that the TC genotype might be a risk factor involved in the possible association with susceptibility to CAD. CONCLUSIONS: The TaqI polymorphism (rs731236) in the coding region may affect the function of the receptor by altering the binding site, which might participate in an inflammatory response and increase the risk for developing susceptibility to CAD.

Association of Vitamin D receptor gene variations with Gastric cancer risk in Kashmiri population.

Vitamin D receptor (VDR) mediates cellular processes like cell cycle arrest and apoptosis which effect cancer susceptibility. VDR single nucleotide polymorphisms (SNPs) have a significant influence on functioning of VDR protein and subsequently contribute to the risk of cancer occurrence and progression. The present case-control study was carried out between 2016 and 2020 to investigate the association of VDR BsmI/ApaITaqI SNPs with Gastric Cancer (GC) risk in ethnic Kashmiri population not only for establishing a molecular marker for GC but also to facilitate the outcomes of personalized medicine in future. The polymorphisms of BsmI and ApaI of the VDR gene were evaluated using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism followed by Di-Deoxy Sanger sequencing in 143 GC cases and 150 controls. The mean age (in years) was 53.5 ± 7.92 and 51.2 ± 8.25 and mean Body mass index was 22.68 ± 4.27 kg/m2 and 23.81 ± 3.71 kg/m2 for cases and controls respectively. The mean CEA levels of GC cases was 40.2 ± 10.9 ng/ml. Genotypic distribution of VDR BsmI differed significantly between GC cases and controls (GG vs GA + AA; adjusted P = 0.014) and followed dominant mode of inheritence. Stratification of VDR BsmI revealed that frequency of variant genotype (GA + AA) was significantly higher in Preobese GC cases (P = 0.001), GC patients consuming < 5 cups of salt tea/day (P < 0.0001) and with no family history of gastrointestinal cancer (P = 0.014) compared to healthy controls. ATC haplotype associated with high GC risk. In conclusion, our study suggests that VDR BsmI SNP has a significant association with increased risk of GC especially in preobese population and BsmI/ApaITaqI SNPs significantly decreased the overall survival in GC patients of Kashmiri population.

Vitamin D level, lipid profile, and vitamin D receptor and transporter gene variants in sickle cell disease patients from Kurdistan of Iraq.

INTRODUCTION: Sickle cell disease (SCD) patients are susceptible to the development of vitamin D deficiency (VDD). Vitamin D through binding to vitamin D receptor (VDR) exerts its function and affects gene transcription in target tissues. VDR gene variants affect bone mineral density. METHODS: In a case-control study, 101 SCD patients including 61 sickle cell anemia (SCA), 39 S/ß-thalassemia, and 1 HbS/HbD (SD) along with 110 healthy individuals from Kurdistan of Iraq were studied. The lipid profile, vitamin D level, FokI, and TaqI variants of VDR and group-specific component (GC) were detected using the standard enzymatic method, the immunodiagnostic systems limited EIA kit and PCR-RFLP methods, respectively. RESULTS: Around 93% and 82% of SCA and S/ß-thalassemia patients, respectively, had VDD compared to 83% of healthy individuals. Severe VDD (<10 ng/ml) was detected in 78.7% of patients with HbSS. Plasma levels of total cholesterol, HDL-C, and LDL-C in SCD patients were significantly lower compared to controls. Vitamin D levels were negatively correlated to TG and positively correlated to total cholesterol and HDL-C. The frequencies of the C allele of FokI were 81.7% (p = 0.003), 80.3% (p = 0.034), and 84.6% (p = 0.011) in all SCD, SCA, and S/ß-thalassemia patients, respectively, compared to 69.1% in controls. However, no significant difference was detected comparing the frequencies of VDR TaqI and GC polymorphisms between SCD patients and controls. CONCLUSION: In the present study, we found hypocholesterolemia, high prevalence of VDR FokI C allele, and low vitamin D levels among children and adults with SCD from Kurdistan of Iraq.

The role of TaqI, ApaI and BsmI polymorphisms of VDR gene in lumbar spine pathologies: systematic review and meta-analysis.

PURPOSE: The objective of the present meta-analysis was to evaluate the association between TaqI (rs731236), ApaI (rs7975232) and BsmI (rs1544410) polymorphisms of the VDR gene and lumbar spine pathologies such as lumbar disc herniation and lumbar disc degeneration. BACKGROUND: VDR gene polymorphisms have been reported to be associated with an increased risk of lumbar spine pathologies. MATERIALS AND METHODS: A systematic search was performed up to February 2020 using PubMed, EBSCO and Web of Science databases. We used the keywords and combinations "lumbar disc degeneration," "lumbar disc herniation," "lumbar spine pathologies" and "VDR polymorphism." Subsequently, we performed a meta-analysis with the results of the included studies. RESULTS: We found that the TaqI polymorphism was associated with an increased risk of developing lumbar spine pathologies (recessive model OR 1.25, 95% CI 1.01-1.54) and lumbar disc degeneration (allelic model OR 1.26, 95% CI 1.07-1.48; recessive model OR 1.34, 95% CI 1.06-1.69), but not with lumbar disc herniation. Additionally, ApaI was associated with an increased risk of developing lumbar spine pathologies (heterozygous model OR 1.45, 95% CI 1.06-1.98), but not with lumbar disc herniation or lumbar disc degeneration. CONCLUSIONS: Our findings indicate that TaqI and ApaI polymorphisms of the VDR gene are important risk factors for developing lumbar spine pathologies. Moreover, the TaqI polymorphism is a risk factor for lumbar disc degeneration.

Association Between Bat Vitamin D Receptor 3' Haplotypes and Vitamin D Levels at Baseline and a Lower Response After Increased Vitamin D Supplementation and Exposure to Sunlight.

Objective: The aim of this study was to evaluate the relationship between vitamin D levels at baseline and after 12 weeks of supplementation/exposure to sunlight and VDR genotypes (BsmI, TaqI and ApaI) and haplotypes in a homogeneous population of postmenopausal women. Methods: We made a prospective study in which 151 women were randomized to two groups: One with 1000 mg of calcium and 800 IU vitamin D supplementation (102 women) and a placebo group with neither calcium or vitamin D supplementation (49 women). The follow-up was from May to September 2012.Vitamin D was determined by chemiluminescent immunoassay. Genotypes were determined using the Sequenomi Plexplatform and haplotypes using PHASE software. Results: Baseline (25 ± 10 ng/mlvs.23 ± 9 ng/ml, p > 0.05) and 12-week (32 ± 8 ng/mlvs.29 ± 10 ng/ml, p > 0.05) vitamin D levels were similar between the two groups. The genetic study was made in the total population. There were no differences in baseline and final levels of vitamin D in terms of genotypes and haplotypes, except for the Bat haplotype, whose baseline values were lower (25OHD: 21 ± 10 ng/mlvs. 21 ± 10 ng/ml, p = 0.038). The rate of nonresponders in this group was 15 % (p = 0.001), compared with 9 %, 2 % and 3 % in the other groups. Conclusions: The Bat haplotype was associated with lower baseline levels of vitamin D and a worse response to supplementation and, therefore, may be a risk factor for vitamin D deficiency.

Positive correlation between vitamin D receptor gene TaqI variant and gastric cancer predisposition in a sample of Iranian population.

Gastric cancer is the second cause of cancer-related mortality and the fourth most common cancers worldwide. Owing to the immune modulatory effect of vitamin D in the body, the role of vitamin D receptor gene in vitamin D regulation receives a great deal of research interest. The aim of the current study was to highlight the association between two variants of TaqI and FokI in the vitamin D receptor gene and gastric cancer predisposition in a sample of South Khorasan population. The present investigation consisted of 69 patients affected with gastric cancer and 100 healthy individuals. The genomic DNA was extracted by salting out the protocol from peripheral venous blood. Genotyping of TaqI and FokI variants were performed by PCR-RFLP method. Our findings manifested that TC genotype of TaqI polymorphism was statistically significant between the case and the control groups (p = 0.002). Moreover, the frequency of TC + CC genotypes was statistically significant between the two groups (p = 0.009). Furthermore, we could not find any meaningful association between FokI variant and the participant groups. The present results declared that, in our population, TC genotype of TaqI polymorphism has an association with gastric cancer susceptibility. In addition, more investigation with greater sample sizes is needed to confirm our results.

Vitamin D Receptor Gene Polymorphisms in Serbian Patients With Bronchial Asthma: A Case-Control Study.

Vitamin D and single nucleotide polymorphisms (SNPs) in vitamin D receptor (VDR) gene are potentially involved in the pathogenesis of bronchial asthma (BA); however, precise mechanisms by which vitamin D reduces the inflammation and the role of VDR SNPs in BA are not completely understood. The aim of this study was to examine the possible associations of FokI, BsmI, ApaI, and TaqI SNPs with BA. A total of 168 subjects were screened for VDR SNPs using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The obtained results showed statistically significant differences in the distribution of FokI genotypes (df = 2; P = 0.008) and alleles (P = 0.002; OR = 0.446; 95%CI = 0.264-0.752) between patients and controls. Distributions of BsmI, ApaI, and TaqI genotypes and alleles did not show statistical differences. BsmI, ApaI, and TaqI SNPs are in linkage disequilibrium (LD) in the whole studied group, as well as in BA patients and controls. The strongest LD was observed between BsmI and TaqI (r2 = 0.69 for all subjects in the study; r2 = 0.75 in BA; r2 = 0.64 in controls), while lower values of LD were observed for BsmI and ApaI, and ApaI and TaqI SNPs. This is the first study that examined the association of VDR SNPs (FokI, BsmI, ApaI, and TaqI) in Serbian patients with BA indicating protective effect of FF genotype and F allele of FokI SNP on BA development. J. Cell. Biochem. 118: 3986-3992, 2017. © 2017 Wiley Periodicals, Inc.

Vitamin D receptor gene polymorphisms and the risk of multiple sclerosis: An updated meta-analysis.

BACKGROUND: The association between vitamin D receptor (VDR) gene polymorphisms and multiple sclerosis (MS) has been extensively studied, but results were controversial. METHODS: This meta-analysis aimed to confirm whether VDR gene polymorphisms were associated with MS. Meta-analysis on the association between MS and VDR ApaI, BsmI, TaqI and FokI polymorphisms were conducted using allelic contrast, recessive, homozygotes and dominant models. Data were extracted by standardized forms and odds ratios (OR) with 95% confidence intervals (CI) were calculated using the random effects model if the results were heterogeneous. Stratification analysis by the selected study characteristics were performed to detect potential source of heterogeneity. RESULTS: A total of 21 relevant studies involving 3593 MS patients and 3917 controls were included in the analysis. The association between TaqI polymorphism and MS risk was significant in the homozygous model (p = 0.006) indicated a significant protective effect of TT TaqI genotype. High latitude (40.1-50°N) was also found markedly influenced TaqI polymorphism and MS risk in the recessive and homozygous models (p = 0.045 and p = 0.015, respectively). Additionally, Asian or low latitude (20.1-30°N) people with ApaI homozygous genotype, '> 2013' publication year people in the allele contrast and dominant models of FokI, '> 40 years' age people with BsmI recessive model also indirectly significantly affected the association between VDR gene polymorphisms and MS risk. CONCLUSION: TaqI polymorphism is a significant protective factor for MS. However, the associations between ApaI, FokI and BsmI polymorphisms and MS were found only by study characteristics.

Association of vitamin D receptor gene polymorphisms with breast cancer risk in an Egyptian population.

This study aimed to explore whether genetic polymorphisms in vitamin D receptor are correlated to the breast cancer prevalence in an Egyptian population. Polymerase chain reaction-restriction fragment polymorphism was used to genotype three frequently analyzed vitamin D receptor gene single-nucleotide polymorphisms (rs1544410, rs7975232, and rs731236) and were identified by sequencing analysis. This is the first study that recorded a new single-nucleotide polymorphism in ApaI genotype within an Egyptian population and was registered with the accession number KY859868. The authors found that TC in rs731236, and TG in KY859868 single-nucleotide polymorphism showed significant distribution differences with an increased risk of breast cancer ( p < 0.05, odds ratio = 3.71, 95% confidence interval: 1.04-13.28 and p < 0.001, odds ratio = 7.05, 95% confidence interval: 2.02-24, respectively) compared with the wild-type TT genotype carriers in both single-nucleotide polymorphisms. In addition, the distribution frequencies of haplotypes ACT, GTT, and ATT in the patients group were significant, where ATT haplotype was associated with the highest breast cancer risk among all other haplotypes in the patients group ( p = 0.0023, odds ratio = 1.72, 95% confidence interval: 1.24-2.437). In conclusion, vitamin D receptors ApaI and TaqI confer high breast cancer susceptibility, particularly in Egyptians females carrying haplotype ATT. However, further studies focusing on the vitamin D receptor variants and haplotypes effects on vitamin D and vitamin D receptor concentrations, activities, and functionalities are needed.

Vitamin D Receptor Gene BSMI, FOKI, APAI, and TAQI Polymorphisms and the Risk of Atopic Dermatitis.

BACKGROUND AND OBJECTIVE: The association between vitamin D receptor (VDR) gene polymorphisms and the risk of skin diseases has been widely studied, yet there is only one study on atopic dermatitis. In this study, we aimed to investigate the association between 4 VDR polymorphisms and atopic dermatitis. PATIENTS AND METHODS: This cross-sectional case control study was performed between March 2013 and April 2014 at the University Hospital in Çanakkale, Turkey. Peripheral blood samples were collected in EDTA tubes. DNA extraction was performed using the spin column procedure. The VDR polymorphisms FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) were determined by polymerase chain reaction-restriction fragment length polymorphism analysis in 42 atopic dermatitis patients and 96 healthy individuals from a Turkish population. RESULTS: The VDR rs1544410 polymorphism increased the risk of atopic dermatitis in our Turkish population [OR, 12.2; 95%CI, 0.44-336; P=.05]. The FoqI, TaqI, and ApaI polymorphisms were not significantly associated with atopic dermatitis susceptibility. CONCLUSION: The VDR Fok1, TaqI, and ApaI gene polymorphisms were not associated with the risk of atopic dermatitis in the Turkish population but the BsmI polymorphism was found to increase risk.

Association of vitamin D receptor BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism with the nephrolithiasis susceptibility.

Association of vitamin D receptor (VDR) gene polymorphism with the risk of nephrolithiasis from the published reports is still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and the risk of nephrolithiasis using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 April 2014, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism with nephrolithiasis susceptibility. In this meta-analysis, VDR BsmI, Fok1, TaqI and ApaI gene polymorphism were not associated with nephrolithiasis susceptibility for overall populations and in Caucasians. However, the Fok1 f allele and ff genotype were associated with the risk of nephrolithiasis in Asians, but the FF genotype not. Furthermore, TaqI TT genotype was associated with the risk of nephrolithiasis in Asians, but the t allele and tt genotype not. However, ApaI gene polymorphism was not associated with nephrolithiasis susceptibility in Asians. In conclusion, VDR BsmI, Fok1, TaqI and ApaI gene polymorphism were not associated with nephrolithiasis risk in overall populations and in Caucasians. But, the Fok1 f allele and ff genotype, TaqI TT genotype, ApaI gene polymorphism were associated with the risk of nephrolithiasis in Asians. However, more studies should be conducted to confirm it.

Association of vitamin D receptor Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism with the risk of chronic kidney disease.

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of chronic kidney disease (CKD) from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and the risk of CKD using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Five reports were recruited into this meta-analysis for the association of VDR Fok1, TaqI and ApaI gene polymorphism with CKD susceptibility. In this meta-analysis, VDR Fok1, TaqI and ApaI gene polymorphism were not associated with CKD susceptibility for overall populations and in Caucasians. However, the Fok1 f allele, ff genotype and FF genotype were associated with the risk of CKD in Asians. In conclusion, VDR Fok1, TaqI and ApaI gene polymorphism were not associated with CKD risk in overall populations and in Caucasians. But, the Fok1 gene polymorphism was associated with the risk of CKD in Asians. However, more studies should be conducted to confirm it.