جستجوی مقالات مرتبط با کلیدواژه « vitamin d receptor » در نشریات گروه « پزشکی »

 Genetic polymorphisms are known to play a crucial role in the development of osteoporosis. Vitamin D3 regulates bone homeostasis through the vitamin D receptor (VDR). Reduced VDR activity increases osteoporosis risk.

Study Design: 

A case-control study.

 This case-control study investigated the potential association between six single-nucleotide polymorphisms (SNPs) within the VDR gene (rs11568820, rs4516035, rs2228570, rs1544410, rs7975232, and rs731236) and the occurrence of osteoporosis in Kerman province. The genotypes of the SNPs were analyzed using polymerase chain reaction-restriction fragment length polymorphism, tetra primer amplification refractory mutation system-PCR, and sequencing in two groups of osteoporosis patients (n=40) and controls (n=42). Additionally, the levels of calcium and vitamin D3 in the serum of the patients were measured, and the in silico analysis of the VDR structure and interaction was performed using I-TASSER, ProSA, PROCHECK, GeneMANIA, GTEx, and GPS 6.0.

 None of the patients exhibited calcium or vitamin D3 deficiencies. Among the six SNPs, only the T allele in rs4516035, which leads to a shorter variant called VDRA, showed a significant association with susceptibility to osteoporosis (odds ratio=3.061, P=0.007). The in silico analysis demonstrated that the 3D structure, expression, and post-transcriptional modification of VDRA are distinct from those of the more extended variant, VDRB1. VDRB1 is upregulated in sun-exposed skin, and its interactions with its partners differ from those of VDRA.

 Despite adequate vitamin D levels, the VDRA variant, which has lower activity, could increase the predisposition to osteoporosis in the studied population. These findings clarify the importance of genetic screening for personalized medicine and the effectiveness of prevention and treatment strategies.

Oral squamous cell carcinomas (OSCC) comprise 90-95% of oral cancers. Early diagnosis improved the survival rate of OSCC patients to 80–90%. Oral lichen planus (OLP) is a chorionic inflammatory disease with malignancy potential. The vitamin D receptor (VDR) plays a critical role in the pathogenesis of oral cancer. This study aimed to determine the association between VDR rs7975232 (Apa I) polymorphism and potential susceptibility to OLP and OSCC risks. In this prospective case-control study, a total of 120 blood samples were obtained from OSCC patients (n=29), OLP (n=50), and controls (n=40). VDR rs7975232 polymorphism was studied using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. Statistical analysis was performed with SPSS Version 23 software. Data were expressed as means ± standard deviation (SD). Age, sex, allelic frequency, and genotyping were compared using the chi-square test. A p-value of less than 0.05 was regarded as statistically significant. The disease risk was estimated by Odds ratio (OR) with a 95% confidence interval. A significant age difference was observed between the controls and the OSCC group (p=0.001). A significant difference was observed in Aa and aa genotypes compared with AA between OSCCs and controls. Moreover, dominant (p<0.001), additive (p<0.001), and allelic (p=0.001) models were different between groups. There was a positive association between rs7975232 VDR polymorphism and susceptibility to OSCC. More experimental evidence must reveal the possible association between rs7975232 and the risk of OLP in a larger cohort.

Vitamin D is associated with numerous disorders, including infertility. Accordingly, the goal of this research was to find out the level of vitamin D and messenger RNA (mRNA) expression of vitamin D receptor (VDR) in the sperm of male subjects with unexplained infertility.

Twenty-four unexplained infertile men as the case group and 22 healthy fertile men as the control group were recruited. Vitamin D levels were evaluated in seminal fluid using enzyme-linked immunosorbent assay (ELISA). Afterwards, the swim-up test was performed to isolate motile sperm cells. From these cells, RNA was extracted, complementary DNA (cDNA) was synthesized, and mRNA expression of the VDR gene was evaluated with quantitative real-time polymerase chain reaction (PCR).

A decrease in VDR mRNA expression levels was detected in the case group compared to the control group, but this reduction was not statistically significant (p>0.05). Besides, the level of vitamin D in seminal fluid was not detectable in both groups.

The sperm of unexplained infertile men express VDR gene mRNA, although there was no vitamin D in seminal samples. Hence, vitamin D and VDR signaling might not be effective in the etiopathogenesis of unexplained infertility in men.

The results of case-control studies on the association between vitamin D receptor gene (VDR) polymorphisms and polycystic ovary syndrome (PCOS) are inconclusive.

We aimed to more precisely evaluate the correlation between the ApaI, BsmI, FokI, and TaqI VDR gene polymorphisms and PCOS susceptibility.

PubMed, Scopus, Science Citation Index, and Google Scholar databases were searched to retrieve related reports released up to the end of 2020. To evaluate the association strength of the VDR gene polymorphisms with PCOS risk, pooled ratios (OR) with a 95% confidence interval were determined.

In total, 1,119 subjects (560 PCOS cases and 559 controls) from 7 studies were included which met the inclusion criteria. A statistically significant association between the TaqI polymorphism and PCOS susceptibility was found in the Eastern Mediterranean Regional Office population (T vs. t: OR = 0.715; TT vs. tt: OR = 0.435, p < 0.001; TT vs. Tt+tt: OR = 0.696, p = 0.01; tt vs. TT+Tt: OR = 1.791, p < 0.001). It was found that the ApaI variant was a risk factor in the dominant inheritance model (AA vs. Aa+aa: OR = 1.466, p = 0.01) and the FokI polymorphism was a protective factor in the recessive inheritance model (ff vs. FF+Ff: OR = 0.669, p = 0.04). The VDR BsmI polymorphism did not show association with PCOS susceptibility.

Our meta-analysis revealed that the VDR ApaI in the dominant model, VDR FokI in the recessive model, and VDR TaqI polymorphisms in all genetic models are associated with vulnerability to PCOS. However, further studies with a larger sample size are required.

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 polymorphisms of five vitamin D receptor (VDR) genes (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.

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 polymorphisms of the five VDR genes (categorical variables) all played a role in the explanatory model. A 10-fold cross-validation process was used for model validation.

Participants were divided into three groups based on their sex. 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:75.32% and, AUC:0.748), EcoRV polymorphism in women (accuracy:78.79 %, AUC: 0.794), and TaqI polymorphism in men (accuracy:71.19%, AUC: 0.651).

Model validation of the final tree models demonstrated that the use of CART algorithms could be a valuable technique for identifying individuals with T2D who are at risk for early-onset osteoporosis based on their polymorphism of the studied VDR genes. Our recommendation is to conduct more population-based studies. We hope this study will serve as a basis for future research.

The association of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) and its receptor, vitamin D receptor (VDR), with cancer types have been studied. However, there are controversial findings regarding the association of specific VDR polymorphisms with different kinds of cancers. In the current study, we investigated the association of VDR polymorphisms (Fok1 (rs2228570), ApaI (rs7975232), BsmI (rs1544410), and TaqI (rs731236)) with the risk of gastric cancer in a Kurdish population of Kermanshah in Iran for the first time.

In this case-control study, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used in 99 gastric cancer patients and 100 healthy subjects as controls.

The frequencies of f (FokI), b (BsmI), t (TaqI), and a (ApaI) alleles were: 55.6%, 27.3%, 62.1%, and 44.95% in the patient group, respectively and 42%, 29.5%, 54.5%, and 46.0% in the control group, respectively. Analysis of the results indicated that there was a positive association between the frequency of FokI genotypes with gastric cancer risk (p= 0.021). However, no statistically significant association of BsmI, Taq1, and ApaI polymorphisms of VDR was detected in gastric patients when compared with healthy individuals.

VDR-FokI polymorphism could increase the risk of GC development and predispose to the disease by mechanisms.

Chronic hepatitis B is a necro-inflammatory of the liver parenchyma caused by hepatitis B virus (HBV) infection leading to liver cirrhosis and hepatocellular carcinoma (HCC). Genetic variants including single nucleotide polymorphisms (SNPs) within genes regulating immune response may contribute to the progression of chronic hepatitis B (CHB) infection. This study aimed to examine the genotype distribution of vitamin D receptor (VDR) polymorphism among patients with CHB infection and to study its association with the development of cirrhosis and hepatoma.

This cross-sectional study analysed 75 CHB patients, consisting of 36 CHB patients without cirrhosis, 25 CHB patients with cirrhosis, and 14 CHB patients with hepatoma. VDR polymorphism was examined using the Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) method.

Alanine aminotransferase (ALT) and alpha fetoprotein (AFP) levels did not show any significant differences between study groups, but albumin levels in CHB patients with cirrhosis and hepatoma were significantly lower than CHB patients without cirrhosis (p< 0.05). In contrast, the bilirubin levels in CHB patients with cirrhosis was higher than in CHB patients’ cirrhosis. The most common genotypes of VDR polymorphisms were Ff (57.3%), TT (72%), aa (48%) and bb (74.7%) for Fok1, Taq1, Apa1 and Bsm1 respectively. There was no significant different in the genotype distribution of VDR polymorphism between CHB patients without cirrhosis and CHB with cirrhosis or hepatoma.

This study suggest that VDR gene polymorphism may not contribute to the progression of CHB infection.

Polycystic ovarian syndrome (PCOS) is an endocrine disorder that affects womenchr('39')s fertility and causes alterations such as obesity, insulin resistance, menstrual irregularities, and polycystic ovaries. The results of the studies show that the issue of vitamin D and vitamin D receptor (VDR) is controversial for PCOS susceptibility.

To investigate the association of BsmI polymorphism in the VDR gene with metabolic parameters in obese PCOS women.

In this case-control study, 38 obese subjects with PCOS and 40 unrelated obese individuals were evaluated to determine the allelic and genotypic frequency of BsmI variant by Polymerase Chain Reaction Restriction Fragment Length Polymorphism method. Body Mass Index, parathyroid hormone, phosphorus, and calcium were evaluated in all participants. 

BsmI (rs1544410), (A/G) AA, AG, GG, A, and G percentage of genotypic/allelic frequencies were 65.8, 26.3, 7.9, 78.9, and 21.1 in cases and 57.5, 40, 2.5, 77.5, and 22.5 in controls, respectively. Statistical analysis revealed that the differences in genotypic (p = 0.31)/allelic (p = 0.83) frequencies and dominant (p = 0.45)/recessive (p = 0.35) models between the cases and controls were not significant. This study indicates no association between the BsmI genotypes and metabolic parameters.

It can be concluded that VDR BsmI (rs1544410) Intron 8 (A>G) was not associated with obesity along with PCOS susceptibility in the studied groups.

Vitamin D receptor (VDR) has been identified as a susceptibility gene for several autoimmune diseases. This study was designed to investigate the association of VDR gene polymorphisms with the susceptibility to rheumatoid arthritis (RA).

A case-control study was performed on 130 RA patients and 128 healthy subjects in the north-east of Iran using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique.  

Our findings suggested a significant association of T allele (p=0.01) of TaqI (rs731236), and f allele (p=0.01) of FokI (rs10735810) genetic variants of the VDR gene with RA susceptibility. These significant associations were also found in the T/T genotype of TaqI (p=0.009), and F/f genotype of FokI (P=0.014). The f-T haplotype was more significantly detected in-patients than in healthy controls (p=0.007).

The RA group showed an increase in the f allele and heterozygous F/f genotype and also in the T allele and homozygous T/T and heterozygous T/t genotypes as compared to the control group. Our results demonstrated that polymorphisms of TaqI and FokI in the VDR gene might be involved in the development of RA in an Iranian population.

Pemphigus vulgaris (PV) is an autoimmune bullous disease of the skin and mucous membranes caused by activation and proliferation of T cells, production of Th2 cytokine profile and pathogenic antibodies. Vitamin D is a probable immunodeviator to Th2, which its actions are mediated through the vitamin D receptor (VDR). FokI is the only single nucleotide polymorphism (SNP) leading to VDR protein with a different structure and function. For the first time, we focused on FokI VDR SNP to evaluate its potential role in the genetic susceptibility to PV, particularly in the Iranian population that has a high prevalence of pemphigus. In this case-control study, DNA samples of 122 PV patients and 233 healthy controls were extracted, and FokI genotyping was performed using the PCR-RFLP method. The mean allele frequencies of F and f alleles in the PV and control groups were 75% and 25%, and 78% and 22%, respectively, showing no significant difference. The genotype frequencies for FF, Ff, and ff genotypes in the case group were 57.4%, 35.2%, and 7.4%, respectively. In the control group, the frequencies were 60%, 36%, and 4%, respectively. Statistical analysis showed no significant difference between the two groups. The present study concluded the frequencies of F and f alleles as approximately 77% and 23% in the gene pool of the Iranian population. Additionally, it showed no association between the FokI alleles and PV in this population.

CAD is a major cause of death in worldwide. Both vitamin D (vit D) and Vitamin-D receptor (VDR) gene polymorphisms have been reported to be associated with Coronary artery disease (CAD). Because of high prevalence of vit D deficiency and mortality caused by cardiovascular diseases in our country, Iran, in this study we aimed to determine the frequency of two known VDR gene polymorphisms (BsmI and ApaI) in patients undergoing Percutaneous Coronary Intervention (PCI) in Iranian populations. Blood samples were collected from 150 patients performing elective PCI (102 males and 48 females). VDR genotypes were determined by RFLP method. Serum vit D levels were measured using HPLC method and patients were divided into three groups as follows: subjects with a total vit D concentration 30 ng/ml> were described as normal, 20-30 ng/ml as insufficient and < 20 ng/ml as deficient. Among 150 samples analyzed for ApaI and BsmI polymorphisms the following genotypic frequency was observed: AA 44.67%, AC 44.67%, and CC 10.66% for ApaI and GG 47.33%, GA 37.33%, AA 15.34% for BsmI Levels of active vitamin D could be influenced by both environmental and genetic factors. Our results also revealed that VDR gene polymorphisms (ApaI and BsmI) may vary across different ethnic groups in CAD patients.

The Vitamin D receptor (VDR) polymorphisms are the candidate genetic variants for susceptibility to different disease including autoimmune disorders. In the present study, we aimed to assess the association between VDR polymorphisms and systemic lupus erythematosus (SLE) susceptibility in Southeast Iranian population.

One hundred and twenty‑seven patients with SLE and 139 controls were genotyped for VDR rs2228570, rs731236, and rs7975232 polymorphisms using polymerase chain reaction‑restriction fragment length polymorphism method.

The VDR rs2228570 polymorphism was associated with higher risk of SLE in codominant, dominant, and overdominant models. Moreover, higher risk of SLE was observed in individuals with VDR rs731236 polymorphism in codominant, dominant, overdominant, and allelic models. The tAf haplotype of rs731236/rs7975232/rs2228570 polymorphisms was associated with higher risk of SLE.

In conclusion, VDR rs2228570 and rs731236 polymorphisms and tAf haplotype were associated with SLE risk.

Vitamin D and insulin play an important role in susceptibility to polycystic ovary syndrome (PCOS), and therefore vitamin D receptor (VDR), parathyroid hormone (PTH), and insulin receptor (INSR) gene variants might be involved in the pathogenesis of PCOS.

The present study was designed to investigate the possible associations between polymorphisms in VDR, PTH, and INSR genes and the risk of PCOS.

VDR, PTH, and INSR gene variants were genotyped in 35 women with PCOS and 35 controls using Polymerase chain reaction – Restriction fragment length polymorphism method. Furthermore, serum levels of glucose and insulin were measured in all participants.

No significant differences were observed for the VDR FokI, VDR Tru9I, VDR TaqI, PTH DraII, INSR NsiI, and INSR PmlI gene polymorphisms between the women with PCOS and controls. However, after adjustment for confounding factors, the VDR BsmI “Bb” genotype and the VDR ApaI "Aa" genotype were significantly under transmitted to the patients (p= 0.016; OR= 0.250; 95% CI= 0.081-0.769, and p= 0.017; OR= 0.260; 95% CI= 0.086-0.788, respectively). Furthermore, in the women with PCOS, insulin levels were lower in the participants with the INSR NsiI "NN" genotype compared with those with the "Nn + nn" genotypes (P= 0.045).

The results showed an association between the VDR gene BsmI and ApaI polymorphisms and PCOS risk. These data also indicated that the INSR "NN" genotype was a marker of decreased insulin in women with PCOS. Our findings, however, do not lend support to the hypothesis that PTH gene DraII variant plays a role in susceptibility to PCOS.

The influence of vitamin D receptor (VDR) gene polymorphisms on the regulation of the parathyroid hormone is important in end-stage renal disease (ESRD) patients. We analyzed rs1544410 (BsmI) and rs731236 (TaqI) polymorphisms of VDR gene in hemodialysis patients to determine their relationship with serum intact parathyroid hormone (iPTH).

Ninety hemodialysis patients were included in this study. Patients were classified into four groups according to their serum iPTH level. Polymorphisms of VDR gene were surveyed using polymerase chain reaction-restriction fragment length polymorphism method with BsmI and TaqI enzymes in all the patients.

Patients age ranged between 30 and 60 years (mean ± SD: 36.0 ± 11.4) and period undergoing hemodialysis 80 ± 71 months. Patients were divided into four groups based on the serum concentration of iPTH. The distribution of VDR gene allelic variation for BsmI and TaqI polymorphisms was different between the four groups of uremic patients. Analysis of data revealed a significant correlation between the TaqI variants and serum iPTH level. There was also a correlation between the BsmI variants and serum iPTH level in that patients with the BB genotype were more likely to have a higher serum iPTH level. However, the latter was not statistically significant.

Genotype of the TaqI and BsmI VDR gene polymorphisms is reported in Iranian patients with ESRD. Those with tt or BB genotypes may develop more severe secondary hyperparathyroidism.