Vitamin D Receptor Polymorphisms Research Articles

Vitamin D receptor polymorphisms and vitamin D insufficiency are not associated with sepsis in critically ill children: a case-control study

BackgroundVitamin D is a fat-soluble vitamin that regulates calcium and phosphorous homeostasis to maintain a healthy mineralized skeleton. It can also influence immune responses and has immunomodulatory properties. Vitamin D receptor (VDR) is a nuclear receptor that mediates the activities of the hormonal form of vitamin D. VDR polymorphisms can alter immunity and susceptibility to infections by modulating VDR expression and vitamin D activity. This study aimed to investigate the levels of serum vitamin D as well as four VDR polymorphisms: FokI, BsmI, ApaI, and TaqI in fifty children admitted to intensive care unit (ICU) with a diagnosis of sepsis and one-hundred age- and sex-matched healthy children.MethodsVitamin D levels were measured in serum, in both patients and controls, using an enzyme-linked immunosorbent assay (ELISA) approach. VDR polymorphisms were also studied in both groups using specific restriction enzymes.ResultsVitamin D levels were low in both patients and controls. Moreover, serum levels were unaffected by VDR polymorphisms, and their distribution was similar in both groups. Neither the need for mechanical ventilation or inotropic treatment nor the sepsis outcome was impacted by serum vitamin D levels or VDR polymorphisms.ConclusionIn children admitted to pediatric ICU, neither vitamin D levels nor VDR polymorphisms were associated with sepsis. Further larger studies including different types of sepsis are recommended.

Association of vitamin D receptor polymorphisms with cardiometabolic conditions in Pakistani population.

Apart from bone related effects, vitamin D has roles in immune modulation, hypertension, diabetes and cardiovascular diseases. Metabolic functions of vitamin D are mediated after binding with vitamin D receptor (VDR). VDR polymorphisms affect its physiological functions. Several VDR single nucleotide polymorphisms (SNPs) were reported previously. However, VDR polymorphisms causing influence on cardiovascular and metabolic disorders have not been investigated in the Pakistani population so far. Therefore, the present study was conducted to evaluate the role of VDR polymorphisms (rs2228570 and rs7975232) in the pathobiology of cardiometabolic disorders. In total, 400 cardiometabolic patients and 226 healthy control human adults were enrolled from Faisalabad, Pakistan. Biochemical parameters (serum glucose, liver function test, renal function test and lipid profile) were analyzed by standard kit methods. Genetic analysis was done by ARMS-PCR assay. Data was analyzed in SPSS v20. Regression analysis revealed that GG and AG genotypes of rs2228570 A>G polymorphism significantly increased the risk of hypertension in cardiovascular patients by 5.29 and 5.94 times respectively (GG: OR=5.29, 95% CI=1.63-17.2, p=0.005; AG: OR=5.94, 95% CI=1.70-20.7, p=0.005). However, rs7975232 C>A polymorphism was not correlated with cardiometabolic conditions. In conclusion, GG and AG genotypes of VDR SNP rs2228570 significantly contribute to hypertension in cardiovascular disease patients.

The association between vitamin D receptor polymorphism and phases of chronic hepatitis B infection in HBV carriers in Thailand.

Vitamin D receptor (VDR) polymorphism partly regulates the immune system and is associated with hepatic flare in chronic Hepatitis B virus infection (HBV). Our study identified the association between two distinct phases, VDR polymorphisms and HBV inactive carrier (IC) and chronic hepatitis (CH). Chronic HBV patients were enrolled from February to August 2020. An HBV viral load (VL) < 2,000 IU/ml twice for 6 months apart, with no prior history of HBV treatment, defined the IC phase. Six common polymorphisms in the VDR gene, including CdX-2, GATA, FokI, Bsml, ApaI, and TaqI, were studied using real-time PCR. The different outcomes in allele, genotype, and haplotype frequencies in between groups and linkage disequilibrium (LD) mapping were analyzed. Among 324 enrolled patients, there were 163 patients in IC and 161 patients in CH phases. The mean vitamin D levels were not statistically different between groups. The proportion of allele frequencies of CdX-2 in IC and CH was 53.7% and 62.7% for G allele, and 46.3% and 37.3% for A allele (p 0.019). The proportion of GG genotype of CdX-2 was less frequently found in patients with IC compared to that in patients with CH (27% vs 41%, p 0.028). By multivariate analysis, CdX-2 G/A genotypes were independently associated with IC, with adjusted odd ratio (OR) 1.83 (1.10-3.04), p 0.019. The LD mapping of single nucleotide polymorphisms (SNP) revealed high LD scores in Bsml/ApaI/TaqI (BAT) haplotype in both groups while, CdX-2/GATA and GATA/FokI demonstrated high LD score only in CH group. CdX-2 G/A genotypes were independently associated with IC status in Thai patients with chronic HBV infection. The difference in LD of the CdX-2/GATA and GATA/FokI haplotypes in between groups may represent a non-random selection resulting in the variation of immune control.

Vitamin D Receptor Gene Polymorphisms and the Risk of CIN2+ in Shanxi Population.

Cervical cancer is one of the most common malignancies in women with high morbidity and mortality. Human papillomavirus (HPV) infection is the primary cause of cervical cancer, of which HPV 16 is the predominant. Early detection and effective treatment of cervical precancerous lesions are the key to preventing cervical cancer. Vitamin D receptor (VDR) gene polymorphism is considered to be an important cause of cancer development. Here, we studied the association of VDR polymorphisms (FOKI, BsmI, ApaI, and TaqI) in HPV16-positive cervical intraepithelial neoplasia (CIN)2+ patients. HPV16-positive patients who visited the Colposcopy Clinic of Obstetrics and Gynecology, the Second Hospital of Shanxi Medical University for biopsy due to abnormal HPV and/or Thinprep cytologic test (TCT) from September 1, 2020 to October 1, 2021 were grouped by pathological results. The fasting blood samples were collected and VDR polymorphisms were detected using TaqMan fluorescent probes, and the three sites of BsmI-ApaI-TaqI were subjected to haplotype analysis. FOKI ff genotype (OR = 2.01; 95% CI = 1.12 - 3.59; p = 0.019) and f allele (OR = 1.48; 95% CI = 1.10 - 1.98; p = 0.009) were found to be associated with the risk of CIN2+. TaqI Tt genotype (OR = 2.03; 95% CI = 1.20 - 3.43; p = 0.008), tt genotype (OR = 2.09; 95% CI = 1.09 - 4.02; p = 0.028), and t allele (OR = 1.35; 95% CI = 1.01 - 1.80; p = 0.041) were associated with the risk of CIN2+. No haplotype was associated with CIN2+ risk. According to the results, FOKI and TaqI polymorphisms are associated with CIN2+ risk.

Association between vitamin D receptor polymorphisms and vitiligo susceptibility: An updated meta-analysis.

Vitamin D receptor (VDR) polymorphisms may play an important role in the vitiligo susceptibility. There have been many studies looking at the associations between VDR polymorphisms and vitiligo risk, but the conclusions are still up for debate. This study aimed to determine whether polymorphisms in the VDR are associated to the susceptibility to vitiligo. Vitamin D receptor polymorphisms in vitiligo patients and controls were identified using PubMed/Medline and Embase databases. The relationships between the VDR ApaI, TaqI, BsmI, and TaqI polymorphisms and vitiligo were investigated using meta-analyses of all participants and Asian, Arab, European, and Latin American groups. This meta-analysis included 13 papers with 2034 patients and 2771 controls. In all individuals, there was no link between vitiligo and the VDR ApaI A allele (OR=0.889, 95% CI=0.713-1.109, p=0.298). However, in Asians (OR=0.721, 95% CI=0.553-0.940, p=0.016) but not in Europeans or Arabs, there was a link between the VDR ApaI A allele and vitiligo. Utilizing recessive, dominant, and homozygote contrast models, a link between vitiligo and the VDR ApaI polymorphism was discovered in Asians. Meta-analysis of the VDR BsmI polymorphism showed a significant association between vitiligo and the B allele (OR=0.812, 95% CI=0.686-0.961, p=0.015). In contrast, no connection between vitiligo and VDR polymorphisms was identified for TaqI and FokI polymorphisms. In the Asian population, ApaI and BsmI polymorphisms in VDR have been correlated to vitiligo susceptibility. However, TaqI and FokI polymorphisms in VDR are not associated with vitiligo susceptibility in European, Asian, Arab, and Latin American populations.

Significant association between TaqI and FokI VDR gene polymorphisms and chronic spontaneous urticaria in a Colombian Caribbean population.

Chronic spontaneous urticaria (CSU) is an inflammatory skin disease related to poor quality of life. Previous studies have found that vitamin D deficiency and vitamin D receptor (VDR) TaqI, BsmI, FokI, and ApaI gene single-nucleotide polymorphisms (SNPs) influence immune response and susceptibility to skin disorders. To explore the role of VDR SNPs, and the association of vitamin D serum levels in a sample of Colombian Caribbean CSU patients. Methods: It is a case-control study. A group of CSU patients (n = 100) was compared with healthy individuals as a control group (n = 100). VDR polymorphisms were genotyped by quantitative polymerase chain reaction and Taqman® probes. Allelic, genotypic, and haplotype associations were estimated. Serum vitamin D levels were measured using enzyme-linked-immunosorbent serologic assay. Compared to the control group, the presence of G allele in TaqI and A allele in FokI SNPs of VDR gene was found to be a risk factor for CSU (odds ratio (OR) estimated using logistic regression adjusted by gender: 2.08 and 1.61, respectively, all P values < 0.05). The individuals who carry GCCA haplotype showed decrease in vitamin D levels (11.34 ng/mL; P = 0.002) with the G allele of TaqI and A allele of FokI gene SNPs. We reported for the first time the association of TaqI [rs731236] and FokI [rs2228570] VDR gene SNPs showing as a risk factor for CSU in a sample of multiethnic patients from the Colombian Caribbean population.

Genetic Variants of VDR and PGC-1α Are Not Associated with the Risk of Endometriosis in Indian Women.

An aberrant immunologic mechanism and mitochondrial biogenesis have been suggested to be involved in the pathogenesis of endometriosis. Genetic alterations in the vitamin D receptor (VDR) gene and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) may lead to important defects in gene activation, which principally affect immune function and normal mitochondrial function. Therefore, we hypothesized a possible role of VDR and PGC-1α genes in the pathogenesis of endometriosis and analyzed the association of genetic variants ApaI A/C (rs7975232) and TaqI T/C (rs731236) of VDR and rs8192678 (G/A), rs13131226 (T/C), and rs2970856 (T/C) of PGC-1α gene. This study included a total of 425 reproductive-age women (cases = 200 and controls = 225). Detection of VDR and PGC-1α gene polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism and sequencing analysis. The chi-square test was used to compare allele and genotype frequencies between groups, and a p-value of <0.05 was considered statistically significant. The genotype and allele distribution of both the gene polymorphisms did not show statistically significant association with endometriosis. Our result indicated ApaI A and TaqI T of VDR and GTT of PGC-1α gene as the most common haplotype in Indian women. The data suggest that VDR and PGC-1α gene polymorphisms did not play an important role in the pathogenesis of endometriosis in Indian women studied.

Four common vitamin D receptor polymorphisms and coronary artery disease susceptibility: A trial sequential analysis.

BackgroundStudies on the susceptibility of vitamin D receptor (VDR) polymorphisms to coronary artery disease (CAD) reached controversial results. We performed this study for a more accurate evaluation between the VDR polymorphisms and CAD susceptibility.MethodsPubMed, Embase, CNKI, Wan Fang, and VIP databases were searched. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to evaluate the associations. Trial sequential analysis (TSA) was introduced to estimate the positive associations. The potential functions of the VDR polymorphisms were analyzed based on the SNPinfo and ENSEMBL databases.ResultsThirteen studies were finally included. In the overall analysis, increased CAD risks were observed in the VDR rs1544410 polymorphism and verified by the TSA; for the rs2228570 and rs731236 polymorphisms, significant associations with high heterogeneity were detected; decreased risk was remarkably observed for the rs7975232 polymorphism. In the subgroup analysis, wide associations with reduced heterogeneity were observed in the rs2228570, rs1544410, and rs731236 polymorphisms. The RNAfold analysis indicated the mutant G allele of the rs1544410 polymorphism was easier to disperse from the DNA double helix structure and may have a potential crucial role in the VDR transcription process.ConclusionsOur analysis supports the role of the rs1544410 polymorphism in the VDR gene as a risk factor for CAD. The VDR rs2228570 and rs731236 polymorphisms were associated with increased CAD risks in the White population. Restrict decreased CAD risk was firstly discovered in the rs7975232 polymorphism.LimitationsFirstly, the language was restricted to English and Chinese, which will cause the limited number of studies included; secondly, other unknown polymorphisms in VDR polymorphisms could also be associated the CAD susceptibility, and more case-control studies with comprehensive clinical outcomes and GWAS studies were required; thirdly, the rs1544410, rs7975232 and rs731236 polymorphism are in strong LD, haploid factors with CAD risk need to be considered; fourthly, the mechanisms of the VDR polymorphism on the VDR gene or RNA or protein were not discussed enough, further mechanistic studies are required; at last, genetic factor was the one side for CAD susceptibility, the interaction between environmental risk factors should be considered.

A cross-sectional study to find association of VDR gene polymorphism with non-syndromic congenital ichthyosis and with vitamin D deficiency.

Though development of vitamin D deficiency and rickets in patients with congenital ichthyosis (CI) have recently been observed, yet exact cause of such association is not properly understood. To evaluate association between Vitamin D Receptor (VDR) polymorphism and CI, and to identify risk factors responsible for development of vitamin D deficiency in ichthyosis. In this cross-sectional study, detailed history of patients and controls was noted and certain biochemical investigations were made. Immunohistochemical staining of skin tissue was done for VDR expression in epidermal and dermal region of ichthyosis patients. VDR polymorphism was assessed in all participants. Ninety-six subjects, were recruited. Mean serum vitamin D was significantly lower among ichthyosis patients. Cdx-2 polymorphism was found to be significantly associated with ichthyosis (p = 0.009). Within the diseased group, Fok-1 (p = 0.035), age (p = 0.020) and alkaline phosphatase (ALP) (p = 0.007) emerged as factors which might be associated with vitamin D deficiency. Cdx2 polymorphism was significantly associated with CI patients. Also, association of Fok-1 polymorphism along with age and raised serum ALP levels emerged as potential factors for determining CI-related vitamin D deficiency.

ASSOCIATION OF VITAMIN D RECEPTOR (VDR) VARIANTS, HYDROXYUREA THERAPY, AND CEREBROVASCULAR DISEASE STATUS ON 25-HYDROXYVITAMIN D (25(OH)D) LEVELS IN PATIENTS WITH SICKLE CELL ANEMIA

Vitamin D, through binding to its specific receptor, vitamin D receptor (VDR), executes actions beyond calcium metabolism and impacts sickle cell anemia (SCA) pathophysiology, such as regulating inflammation, vascular tone, and thrombogenesis. Genetic polymorphisms that can potentially disturb VDR function or its levels may modify the vitamin D mechanism and have already been associated with several conditions, including stroke. Therefore, we evaluated the association of 25-hydroxyvitamin D (25(OH)D) levels with VDR gene polymorphisms, hydroxyurea (HU) therapy, and cerebrovascular disease (CVD) in an SCA cohort. 25(OH)D levels were determined using the automated microparticle chemiluminescence method in 45 non-related SCA patients (55.5% males). Genotyping for functional FokI (rs2228570) and Cdx-2 (rs11568820) VDR polymorphisms was performed with TaqMan fluorogenic probes. Nonparametric Mann-Whitney and Kruskal-Wallis tests, followed by Dunn's multiple comparisons post-test, were used to analyze continuous variables. The median 25(OH)D levels were 20.9 ng/mL (range, 10 – 37.2 ng/mL). 18 patients (40%) had vitamin D deficiency (25(OH)D < 20ng/mL), 22 (49%) had insufficient levels (25(OH)D 20 - 30 ng/mL) and 05 (11 %) had sufficient levels (25(OH)D > 30 ng/mL). No difference was observed in 25(OH)D levels according to FokI and Cdx-2 genotypes (p > 0.05). However, 25(OH)D levels were decreased in patients with CVD (p = 0.026) and patients under hydroxyurea (HU) therapy (p = 0.005). Considering patients under HU therapy, individuals with variant TT- FokI genotype had lower levels of 25(OH)D (median: 13.9 ng/mL) when compared to those with CC/CT genotypes (median: 20.2 ng/mL; p = 0.03). In the group of individuals without HU therapy, this finding was not observed (p > 0.05). Although not statistically significant, patients with CVD and TT- FokI genotype had lower levels of 25(OH)D (median: 12.3 ng/mL) when compared to individuals with CC/CT genotypes (median: 20,8 ng/mL; p = 0.075). Despite the influence of HU in 25(OH)D levels has already been addressed with conflicting results, the mechanism that might explain these associations is not yet known. Moreover, previous findings indicate that the effect of functional VDR variants can be influenced by vitamin D status. Therefore, under the influence of factors that affect vitamin D levels, the defective VDR isoform, resulting from the FokI polymorphism, possibly accentuates the 25(OH)D deficiency, contributing to an adverse outcome. In summary, 25(OH)D levels are reduced in SCA patients with CVD and those under HU therapy. Further studies are required to determine the mechanism underlying HU and 25(OH)D levels associations and the effect of vitamin D supplementations in patients with CVD in SCA, especially those under HU therapy.

Vitamin D receptor polymorphism and prostate cancer prognosis.

Prostatic epithelial cells synthesize the active form of vitamin D (1,25-dihydroxyvitamin D3), which participates in regulating prostate growth. Calcitriol, a synthetic form of vitamin D3, exhibits antiproliferative and prodifferentiation activities in prostate cancer. The function of 1,25-dihydroxyvitamin D3 is mediated by its binding to vitamin D receptor (VDR). VDR forms a heterodimer, typically with retinoid X receptor, to regulate vitamin D target genes. We evaluated the relationship between VDR polymorphism and clinical characteristics associated with prostate cancer risk and prognosis among Egyptian men. This case-control study included 2 groups of patients: group A, a control group of 50 subjects with benign prostate hyperplasia, and group B, 50 subjects newly diagnosed with prostate cancer. All participants performed complete blood count, liver and kidney function tests, prostate specific antigen measurement, histopathological analysis and immunohistochemistry for Dickkopf Homolog 3. Restriction fragment length polymorphism-polymerase chain reaction as performed to detect VDR polymorphism. Patients with prostate cancer and controls showed a significantly different CA genotype frequency (p = 0.007). Furthermore, prostate-specific antigen levels were significantly different in different genotypes in patients with prostate cancer (p < 0.001). Finally, T stage and the VDR ApaI C/A polymorphism were significantly associated (p < 0.041). The VDR ApaI C/A polymorphism may be a diagnostic and prognostic marker for prostate cancer in Egyptian men.

Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19

BackgroundGiven the sparse data on vitamin D status in pediatric COVID-19, we investigated whether vitamin D deficiency could be a risk factor for susceptibility to COVID-19 in Egyptian children and adolescents. We also investigated whether vitamin D receptor (VDR) FokI polymorphism could be a genetic marker for COVID-19 susceptibility.MethodsOne hundred and eighty patients diagnosed to have COVID‐19 and 200 matched control children and adolescents were recruited. Patients were laboratory confirmed as SARS-CoV-2 positive by real-time RT-PCR. All participants were genotyped for VDR Fok1 polymorphism by RT-PCR. Vitamin D status was defined as sufficient for serum 25(OH) D at least 30 ng/mL, insufficient at 21–29 ng/mL, deficient at <20 ng/mL.ResultsNinety-four patients (52%) had low vitamin D levels with 74 (41%) being deficient and 20 (11%) had vitamin D insufficiency. Vitamin D deficiency was associated with 2.6-fold increased risk for COVID-19 (OR = 2.6; [95% CI 1.96–4.9]; P = 0.002. The FokI FF genotype was significantly more represented in patients compared to control group (OR = 4.05; [95% CI: 1.95–8.55]; P < 0.001).ConclusionsVitamin D deficiency and VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents.ImpactVitamin D deficiency could be a modifiable risk factor for COVID-19 in children and adolescents because of its immune-modulatory action.To our knowledge, ours is the first such study to investigate the VDR Fok I polymorphism in Caucasian children and adolescents with COVID-19.Vitamin D deficiency and the VDR Fok I polymorphism may constitute independent risk factors for susceptibility to COVID-19 in Egyptian children and adolescents.Clinical trials should be urgently conducted to test for causality and to evaluate the efficacy of vitamin D supplementation for prophylaxis and treatment of COVID-19 taking into account the VDR polymorphisms.

Association between vitamin D receptor gene polymorphisms and fibrosis susceptibility in Greek patients with HCV infection.

Hepatitis C virus (HCV) infection is a prime cause of chronic hepatitis worldwide, that often silently progresses to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Notably, the majority of individuals infected with HCV develop symptoms at late stages, often associated with liver damage that cannot revert after virus clearance. Thus, current antiviral therapy alone is rather insufficient to eliminate the global burden of HCV in the near future.During the past few years, vitamin D deficiency as well as certain single nucleotide polymorphisms in the vitamin D receptor (VDR) gene have been associated with liver fibrosis. Therefore, the aim of the present study was to investigate the possible correlation between VDR polymorphisms ApaI (rs7975232) and TaqI (rs731236) and the fibrosis stage of patients with HCV infection from Thrace, Greece. Eighty-one patients with HCV infection underwent transient elastography for the assessment of their fibrosis stage, and PCR-restriction fragment length polymorphism (RFLP) genotyping for VDR ApaI and TaqI polymorphisms. VDR genotypes were then statistically associated with the patients' fibrosis stage using ordinal regression models. Non-cirrhotic stages were positively correlated with TaqI TT genotype (p=0.003) and negatively correlated with TaqI TC genotype (p=0.007). In the presence of Hardy-Weinberg equilibrium and linkage disequilibrium between the two VDR polymorphisms, mild fibrosis stages (F0-2) were correlated with ApaI/TaqI GG/TT (p=0.002) and TG/TT (p=0.008) genotypes, while cirrhotic stage F4 was associated with ApaI/TaqI TG/TC genotype (p=0.038). TaqI TT and ApaI/TaqI GG/TT, TG/TT and TG/TC genotypes could be explored as prognostic genetic markers for fibrosis susceptibility in HCV patients.

An application of CART algorithms for detection of an association between VDR polymorphisms and reduced bone density in individuals with type 2 diabetes: a population-based cross-sectional study

Introduction: An important part of preventing major common diseases is identifying genetic factors that contribute to their occurrence. For the first time in our knowledge, we investigated the association between five polymorphisms of vitamin D receptor (VDR) gene (ApaI, BsmI, FokI, EcoRV, and TaqI) and low bone density/osteopenia/osteoporosis in individuals with type 2 diabetes using classification and regression tree (CART) algorithms. Methods: Data from 158 participants with T2D were used to develop the CART analysis. The binary output variable was "bone state" with low or normal values. Age and BMI (continuous variables), vitamin D deficiency (yes/no), and gender (binary variables), as well as the studied polymorphism of the VDR gene (categorical variables) all played a role in the explanatory model. A 5-fold cross-validation process was used for model validation. Results: Participants were divided into three groups: men, women, and both sexes. In all groups, age was the major factor predicting the low state in the final obtained tree model. The second most significant predictor in each model was BMI in both sexes (accuracy:75.30% ± 2.80%, AUC: 0.740 ± 0.064), EcoRV polymorphism in women (accuracy: 80.79% ± 6.58%, AUC:0.785 ± 0.063), and TaqI polymorphism in men (accuracy: 76.36% ± 3.05%, AUC:0.706 ± 0.125). Conclusion: Model validation of the final tree models demonstrated that the use of CART algorithms could be an acceptable technique for risk factors of osteoporosis among individuals with T2D. Our recommendation is to conduct more population-based studies. We hope this study will serve as a basis for future research.

Genetic variations of vitamin D receptor and vitamin D supplementation interaction in relation to serum vitamin D and metabolic traits: a systematic review and meta-analysis.

Background: It is now becoming increasingly recognized that the effects of vitamin D supplementation may vary by several factors including vitamin D deficiency status, ethnicity, and/or the presence of genetic variants, which affect individual responses to supplementation. This study investigates the interaction between metabolic traits and circulating 25-hydroxyvitamin-D (25OHD) concentration with 4 polymorphisms of vitamin D receptor (VDR) including BsmI, ApaI, TaqI, FokI, and vitamin D supplementation. Methods: A systematic review and meta-analysis of papers until August 2021 on PubMed, The Cochrane Library, Scopus, Web of Science, Google Scholar, ProQuest, Science Direct, and Embase about the association between functionally relevant VDR variants and vitamin D supplementation on circulating 25OHD and metabolic traits. Results: A total of 2994 cases from 16 randomized controlled trial (RCT) studies were included in meta-analyses. There were no significant changes in the serum concentrations of 25OHD and metabolic traits after vitamin D supplementation in different variants of BsmI, ApaI, TaqI, and FokI polymorphism in the VDR gene in the overall analysis (p>0.05). However, the results showed there is significant interaction between these above VDR polymorphisms and vitamin D supplement on serum 25OHD level after subgroup analyses based on the study duration, gender, age, BMI, health status, Hardy-Weinberg Equilibrium, PCR, and race (p<0.05). Conclusions: The present meta-analysis demonstrates that the effect of vitamin D supplementation on serum 25OHD and metabolic traits is independent of genetic variants of the VDR gene (BsmI, ApaI, TaqI, and FokI). However, future trials should consider inter-individual differences and, in particular, should aim to clarify whether certain subgroups of individuals may benefit from vitamin D supplementation in the context of metabolic health.

The interactive effect of vitamin D3 supplementation and vitamin D receptor polymorphisms on weight and body composition in overweight women with hypovitaminosis D: a randomized, double-blind, placebo-controlled clinical trial.

Different responses to vitamin D supplementation may be due to genes involved in vitamin D metabolism, including the vitamin D receptor (VDR) gene. The present study aimed to determine the interactive effect of vitamin D supplementation and VDR polymorphisms, including FokI (rs2228570) and BsmI (1544410) on weight and body composition in overweight women with hypovitaminosis D. This study comprised two phases: a double-blind, randomized and a before-after clinical trial. In the first phase, 50 healthy overweight women aged 20-45 years with hypovitaminosis D were randomly categorized into intervention and control groups and were given 50000 IU/w vitamin D3 or placebo for 12 weeks. In the second phase, 75 women received 50000 IU/w of vitamin D3 for 12 weeks. All variables were measured at baseline and after 12 weeks. Circulating 25(OH)D was measured using an ELISA kit. Anthropometric indices were calculated according to standard protocol (WHO-TRH-854). Body composition was determined using the body impedance analysis method. The VDR polymorphisms were detected using the PCR sequence. Supplementation resulted in a significant increase in the level of 25(OH)D in the intervention group but did not affect the anthropometric profile of the subjects. When considering FokI genotypes, carriers of the FF genotype had higher fat mass reduction than carriers of Ff+ff genotypes.

Thyroid gland dysfunction and vitamin D receptor gene polymorphism in keratoconus

ObjectivesTo detect the serum level of thyroid hormones, vitamin D and vitamin D receptors (VDR) polymorphism in keratoconus (KC) patients and to identify the association between vitamin D deficiency and thyroid dysfunction in KC.MethodsThis cross sectional study included 177 KC patients with no thyroid disorders compared to 85 healthy controls with normal corneal tomography. Measurements of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free tetraiodothyronine (FT4) and serum 25-OH vitamin D were done using Enzyme linked immusoassay (ELISA test). VDR polymorphisms were tested including [Taq I (rs731236), Apa I (rs7975232) and Bsm I (rs1544410)] using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).ResultsAn increase in frequency of thyroid disorders (P = 0.04), decrease in serum 25(OH) vitamin D level (P < 0.001), Taq 1 and tt genotype (P < 0.001) were significantly distributed in KC patients. A significantly higher serum 25(OH) vitamin D level was reported in TT genotype, while insufficient level was more common in Tt genotype (P < 0.001). A deficient serum 25(OH) vitamin D level was predominant in tt genotype (P < 0.001). A 95% confidence interval was in TSH (1.603, 2.946), FT4 (24.145, 77.06), hypothyroidism (1.062, 67.63), insufficient (2.936, 11.643) and deficient vitamin D (5.283, 28.704) and all were significant risk factors for KC with (P < 0.05).ConclusionsBoth thyroid disorders and low vitamin D are potential factors for KC development. Studying VDR at the molecular level provides interesting avenues for future research toward the identification of new KC cases.

Vitamin D, Vitamin D-Binding Proteins, and VDR Polymorphisms in Individuals with Hyperglycaemia.

Vitamin D reportedly plays an important role in the pathogenesis of diabetes mellitus; however, this role is unclear and debated. This study investigated the association between 25(OH) vitamin D, vitamin D-binding proteins, and vitamin D receptor (VDR) polymorphisms in healthy individuals and those with prediabetes and type 2 diabetes mellitus (T2D) from South Africa. A cross-sectional study was conducted involving subjects of mixed ancestry aged ≥20 years. Males presented with higher mean 25(OH) vitamin D levels than females, while females exhibited significantly higher serum vitamin D-binding protein levels. Significant differences in mean 25(OH) vitamin D levels were observed in normo-glycaemic, prediabetes, screen-detected DM, and known DM individuals. Vitamin D receptor SNPs Fok1 and Taq1 were not associated with glycaemic status. Fok1 was not associated with 25(OH) vitamin D deficiency, while Taq1 was associated with vitamin D insufficiency. This study showed a high prevalence of vitamin D deficiency/insufficiency in this South African population, with decreased vitamin D levels observed in hyperglycaemic individuals, which was not linked to either vitamin D-binding protein or polymorphisms in Fok1 of the VDR gene. These results may be used as a platform for further research into diagnosis and treatment of hyperglycaemia.

VDR gene polymorphisms are associated with the increased susceptibility to COVID-19 among iranian population: A case-control study.

Coronavirus disease 2019 (COVID‐19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), but the pathogenesis is unclear. Host genetic background is one of the main factors influencing the patients' susceptibility to several viral infectious diseases. This study aimed to investigate the association between host genetic polymorphisms of two genes, including vitamin D receptor (VDR) and vitamin D binding protein (DBP), and susceptibility to COVID‐19 in a sample of the Iranian population. This case‐control study enrolled 188 hospitalized COVID‐19 patients as the case group and 218 suspected COVID‐19 patients with mild signs as the control group. The VDR (rs7975232, rs731236 and rs2228570) and DBP (rs7041) gene single nucleotide polymorphisms (SNPs) were genotyped by Polymerase Chain Reaction Restriction – Fragment Length Polymorphism (PCR‐RFLP) method. A significant association between rs2228570 SNP in the VDR gene and the susceptibility of COVID‐19 was found between case and control groups. The CT genotype (Heterozygous) of rs2228570 C > T polymorphism showed significant association with a 3.088 fold increased odds of COVID‐19 (p < .0001; adjusted OR: 3.088; 95% CI: 1.902–5.012). In addition, a significant association between CC genotype of rs2228570 CT polymorphism and increased odds of COVID‐19 in male and female groups (p = .001; adjusted OR: 3.125; 95% CI: 1.630–5.991 and p = .002; adjusted OR: 3.071; 95% CI: 1.485–6.354 respectively) were determined. Our results revealed no significant differences in the frequency of genotype and allele of VDR (rs7975232 and rs731236) and DBP (rs7041) between SARS‐CoV‐2‐infected patients and controls (p > .05). Our results showed that polymorphism of VDR (rs2228570) probably could influence individual susceptibility to COVID‐19. The polymorphisms of VDR (rs7975232 and rs731236) and DBP (rs7041) were not associated with SARS‐CoV‐2 infection susceptibility.

Prediction of the cognitive impairment development in patients with autoimmune thyroiditis and hypothyroidism.

Objective. The aim of the present work is to define the risk factors that can affect the presence of a cognitive impairment and analyze the associations of the brain-derived neurotrophic factor (BDNF) gene polymorphism (rs6265), vitamin D receptor (VDR) gene polymorphism (rs2228570), and N-methyl-D-aspartate (NMDA) receptor gene polymorphism (rs4880213) with the cognitive impairment in patients with autoimmune thyroiditis and hypothyroidism in the Western Ukraine population and predict the development of cognitive disorders in these patients. Methods. The study involved 153 patients with various forms of thyroid pathology (hypothyroidism, autoimmune thyroiditis, elevated serum antibodies anti-thyroglobulin and anti-thyroid peroxidase). Cognitive impairment in the examined patients was evaluated based on the results of the Mini-Mental State Examination (MMSE) test. BDNF, GRIN2B, and 25-OH Vitamin D levels in the serum of the patients and healthy individuals were quantified using highly sensitive commercial enzyme-linked immunosorbent assay kits. Genotyping of the VDR (rs2228570), BDNF (rs6265), and NMDA receptor (rs4880213) gene polymorphism was performed using TaqMan probes and Taq-Man Genotyping Master Mix (4371355) on CFX96™Real-Time PCR Detection System. Polymerase chain reaction (PCR) for TaqMan genotyping was carried out according to the kit instructions. Results. Strong direct relationship between the "Level GRIN2B" and cognitive impairments (p=0.006) was established after evaluating the complex model based on the values of the regression coefficient. An increase in the likelihood of cognitive impairment by 24.898-fold (p=0.012) was seen after assessing the effect of the CT rs6265 genotype. In addition, direct relationship between the influence of the TT rs6265 genotype and an increase in the likelihood of cognitive impairment by a factor of 21.734 (p=0.024) was also established. Conclusion. The present data indicate that the BDNF, TSH, fT4, and vitamin D levels prognostically belong to the significant indicators of the cognitive impairment development.