TaqI Polymorphisms Research Articles

Some genetic differences in patients with rheumatoid arthritis

ObjectiveVitamin D is important for bone and cartilage metabolism. Changes in vitamin D blood level may be related to pathological disorders such as rheumatoid arthritis (RA). The main aim of this study is to investigate the association between RA and the vitamin D receptor (VDR) genes FokI and TaqI polymorphisms. One hundred RA patients and fifty healthy matched controls were assessed for VDR FokI and TaqI genotyping. Intact parathyroid hormone (PTH) and calcium (Ca) levels were measured, categorized, and compared between the cases and control groups.ResultsWe found that the FokI genotype frequencies for the RA cases and control groups were FF:Ff:ff = 46%:52%:2% and 50%:50%:0%, respectively (P = 0.76). The TaqI genotype frequencies for the RA cases and control groups were TT:Tt:tt = 45%:44%:11% and 42%:42%:16%, respectively (P = 0.69). A statistically significant high serum PTH level was associated with the ff genotype (p = 0.03), and a significantly low serum Ca level was associated with the TT genotype (p = 0.003). In comparison with controls, no influence of VDR FokI and TaqI genotypes on RA susceptibility or risk was demonstrated.

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

BackgroundDetermining 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.MethodsThis 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.ResultsRegarding 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.ConclusionIn association with vitamin D deficiency, VDR gene FokI polymorphism, not TaqI, is a genetic risk factor for complicated pneumonia in Egyptian children.

A Family-based Association Test of the VDR Gene in Proximal Spinal Muscular Atrophy

Different factors may be involved in the clinical heterogeneity of spinal muscular atrophy disease. The vitamin D receptor (VDR) might be a candidate gene for this disease. Our study aimed to assess the preferential transmission of VDR polymorphisms from parents to SMA children. We genotyped 261 subjects (87 SMA nuclear families) for VDR FokI, BsmI, ApaI, and TaqI polymorphisms. The transmission of the genetic marker was estimated with Plink and FBAT software. It detected a preferential transmission of the rs731236 and rs7975232 variants to SMA1 patients and of rs1544410 variants to SMA2 patients. The variants of rs2228570 were preferentially transmitted to parents of all SMA patients. Haplotype analysis identified that haplotypes C-C-G-A and T-A-A-G seem to be involved in the booth type of SMA whereas the impact of T-A-A-A seems to be limited only to SMA2. Strong linkage disequilibrium (LD) between rs7975232 and rs1544410 was detected in samples from parents. Even though we investigated a small number of nuclear families the results suggest a potential link between VDR polymorphisms and SMA disease.

TaqI polymorphism of the vitamin D receptor gene in children with growth hormone deficiency

Background. The nuclear receptor for vitamin D mediates most of the biological functions of this vitamin. It belongs to the steroid hormone receptor family, the gene for which (vitamin D receptor — VDR) is located on chromosome 12q13.1. Genetic variability has been reported in the VDR gene, in which more than 470 single nucleotide polymorphisms have been identified. One of the most common polymorphisms in the VDR gene is rs731236 (TaqI). The purpose was to study the TaqI polymorphism of the VDR gene in children with growth hormone deficiency (GHD). Materials and methods. The TaqI polymorphism of the VDR gene (rs731236) was determined using the polymerase chain reaction, followed by analysis of the length of restriction fragments detected by agarose gel electrophoresis in 28 prepubescent children with GHD. Results. In the group of patients with GHD, the proportion of heterozygotes for T/C TaqI polymorphism of the VDR gene (rs731236) is 1.28 times higher than among healthy individuals. There were 0.68 and 0.90 times fewer patients carrying T/T and C/C genotypes than in the control group. The presence of a homozygous TT genotype increases the risk of developing GHD, but not significantly (odds ratio (OR) = 1.89, 95% confidence interval (CI) 0.66–5.39; p = 0.23), and the presence of a homozygous CC genotype is protective (OR = 0.75, 95% CI 0.17–3.22; p = 0.70). When analyzing alleles in patients with GHD, the following data were obtained: carriage of the T allele for the polymorphic loci TaqI rs731236 of the VDR gene is associated with the risk of GHD (OR = 1.24, 95% CI 0.65–2.36; p = 0.52) but not significantly. The ratio of allele (pТ = 0.554, qС = 0.446) frequencies practically does not differ from 1 : 1, which indicates the preservation of allele frequencies in the Ukrainian population. Conclusions. In children with GHD, the proportion of the T/C genotype is 1.28 times higher than in the group of healthy persons. The presence of a homozygous TT genotype increases the risk of developing GHD but not significantly (OR = 1.89, 95% CI 0.66–5.39; p = 0.23). Carriage of the T allele for the polymorphic locus TaqI rs731236 of the VDR gene is associated with the risk of the growth hormone deficiency (OR = 1.24, 95% CI 0.65–2.36; p = 0.52) but not significantly.

Vitamin D status, vitamin D receptor gene polymorphism, and haplotype in patients with cutaneous leishmaniasis: Correlation with susceptibility and parasite load index.

CL endemicity was reported worldwide including in Saudi Arabia, imposing a major challenge on the health authorities. Vitamin D and its receptor (VDR) are key modulators of the immune response where the VDR is expressed. A remarkable lack of data exists in humans about the contribution of vitamin D and polymorphisms of the VDR gene in protozoan infections, especially cutaneous leishmaniasis (CL). This is the first work conducted to assess the relationship between vitamin D status, polymorphisms of the VDR gene (BsmI, ApaI, TaqI, and FokI), and VDR haplotype with parasite tissue load and susceptibility to CL. Fifty-two patients with confirmed CL (21 patients receiving vitamin D medication and 31 patients not receiving it) and 46 control subjects participated in this cross-sectional investigation. VDR genotyping was determined by restriction fragment length polymorphism analysis. Serum levels of 25-OH vitamin D were assessed using the ELISA method in all participants. The skin biopsy quantified the parasite load based on the Ridley parasitic index. The mean serum level of 25-OH vitamin D in CL patients who were not receiving vitamin D therapy was significantly lower compared to CL patients on vitamin D therapy and controls (p <0.001 for both) and CL patients with no history of vitamin D therapy had a significantly higher frequency of vitamin D deficiency compared to CL patients on vitamin D therapy and controls (p < 0.05). Compared to CL patients with no history of vitamin D therapy, CL patients receiving vitamin D therapy had a significantly lower mean size of the lesion and RPI (p = 0.02, .03 respectively). The frequency of genotype "aa" and its "a" allele in ApaI SNP of VDR was significantly lower in CL patients compared to controls (p = 0.006 and 0.03 respectively). However, patients with CL had a considerably greater frequency of the "A" allele than the controls (p = 0.03), suggesting its role in CL susceptibility. There was no statistically significant difference between the two groups in the genotype and allele frequency distributions of BsmI, TaqI, and FokI (p > 0.05). When compared to controls, CL cases had a considerably greater frequency of the "B-A-T-F" haplotype (p = 0.04), and a significantly lower frequency of the "B-a-T-F" haplotype (p = 0.01) suggesting that these haplotypes may have the potential susceptibility or protection against CL respectively. The "Aa" genotype in ApaI SNP of VDR had considerably lower levels of vitamin D with higher parasite load compared to the "AA" and: aa" genotypes (p = 0.02,0.02 respectively). A significant negative correlation was found between the parasite load and 25-OH vitamin D levels (r2 = -0.53, p< 0.001). According to these findings, vitamin D levels and "ApaI" VDR gene polymorphisms could affect the parasite load and susceptibility to infection, whereas BsmI, FokI, and TaqI polymorphisms did not. Correction of vitamin D levels may aid in CL management.

Vitamin D receptor gene polymorphisms in Iraqi Arab children with autism spectrum disorder and serum vitamin D and vitamin D receptor levels

The association between a vitamin D receptor gene (VDR) and autism spectrum disorder (ASD) in some ethnic groups is still inconclusive, among Iraq's Arab population, this association hasn't been highlighted as yet. Two hundred and eighteen ASD children were examined; 171 males and 47 females (mean age 6.91 ± 4.11 years). The control group was 211; 162 were males and the rest were females. The purpose of this study was to identify a correlation between four single nucleotide polymorphisms (SNPs); TaqI (rs731236), FokI (rs2228570), ApI (rs7975232) and BsmI (rs1544410) in the VDR using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) with susceptibility to childhood ASD. An Enzyme-linked immunosorbent assay (ELISA) was used to assess serum vitamin D and vitamin D receptor levels. There was a statistically significant increase in the prevalence of the CC genotype and the C allele in VDR TaqI (rs731236) among patients compared to controls [15.6% vs. 1.8%, OR = 4.39, 95% CI = 2.18–8.81, p = 0.001] and [34.6% vs. 23.2%, OR = 1.74, 95% CI = 1.30–2.32, p = 0.001] respectively. Furthermore, the frequency of the variant CC genotype and C allele of the FokI in codominant model increased significantly in ASD patients than in the controls [23.8% vs. 6.5%, OR = 4.20, 95% CI = 2.22–7.96, p = 0.001] and [34.2% vs. 20.9%, OR = 1.97, 95% CI = 1.44–2.67, p = 0.001] respectively. In addition, the frequency of CC genotype increased significantly in the recessive models of TaqI (rs731236) and FokI (rs2228570) in ASD patients compared to controls (15.6% vs. 1.8% OR = 9.56, 95% CI = 3.32–27.4, p = 0.001) and (27.2% vs. 6.7%, OR = 4.40, 95% CI = 2.35–8.23, p = 0.001), respectively. Mean serum VDR levels decreased significantly in ASD patients with both CC genotypes of TaqI (rs731236) than TT genotypes (P = 0.026) and in CC genotypes of FokI (rs2228570) than TT genotypes (p = 0.012). Moreover, vitamin D and VDR levels were considerably lower in ASD patients than in controls respectively (p = 0.0001). Our findings demonstrate that specific polymorphisms TaqI (rs731236) and FokI (rs731236) in VDR were high risk factors for developing childhood ASD in the Iraqi Arab population.

A Correlative Study of Vitamin D Receptor Variants Fok1, Apa1, Bsm1, and Taq1 Polymorphism and Vitamin D Deficiency with Higher Risk Ratio of Coronary Artery Disease in Female Population

Abstract No studies are available on single nucleotide polymorphisms (SNPs) of the VDR gene in association with coronary artery disease (CAD) in women. The study aimed to investigate the association between SNPs in the VDR regions Fok I (rs10735810), Bsm I (rs1544410), Apa I (rs7975232), and Taq I (rs731236) and its associated risk of CAD in female patients. This prospective case-control study included 100 women diagnosed with CAD and age-matched healthy controls. The association between 1,25-dihydroxy vitamin D levels and VDR polymorph was assessed. In cases, the genotype ‘ff’ was reduced (14%) in co-dominant (OR, 0.13; CI, 0.03–0.65, p=0.0018) and recessive (OR, 0.11; CI, 0.02–0.54, p=0.0018) models. The ‘Ff’ genotype frequency in the over-dominant model was significantly higher (15%) in some cases (OR, 2.58; CI, 1.04–6.41, p=0.031). The frequency of genotype ‘Bb’ was increased (14%) in co-dominant (OR, 2.24; CI, 0.83–6.01, p=0.029) and over-dominant (OR, 2.65; CI, 1.01–6.94, p=0.035) cases. Women with CAD had a significantly lower frequency (14%) of the ‘bb’ genotype in both co-dominant (OR, 0.48; CI, 0.19–1.17, p=0.029) and recessive models (OR, 0.40; CI, 0.17–0.95, p=0.039). VDR genotypes such as Aa+aa, BB+Bb, Aa, Bb, FF+Ff, Tt+tt, aa, Ff, and tt were associated with an increased risk of CAD, and serum vitamin D levels were lower. Alleles ‘a’, ‘B’, and ‘t’ increase CAD risk in women. Subjects with genotypes (BB/Bb), (Tt/tt), and (FF) have a 2-fold, 2.6-fold, and 3-fold increased risk of low 25(OH)D3 levels. We found a statistically significant association between VDR polymorphisms and 25(OH)D3 levels for Taq I and Bsm I genotypes in females with CAD.

Evaluation of the Relationship between Vitamin D Receptor Gene Polymorphisms and Multiple Sclerosis Patients Who Responsive or non-Responsive to Treatment with Beta Interferon

Introduction: Multiple Sclerosis is a chronic, inflammatory disorder of the central nervous system, which leads to demyelination of nerves. Treatment with interferon beta is one of the best approaches to reduce recurrence and progression of the disease. The aim of this study is to search for the relationship between 4 polymorphisms FokIrs10735810, TaqIrs731236, ApaIrs797532 and BsmIrs1544410 located in the vitamin D receptor in MS patients responsive and non-responsive to interferon beta treatment and pave the way for the correct and fast administration of the appropriate drug, as well as reducing time, cost and lack of success in treatment.&#x0D; Methods: The type of study is observational and the study method is case-control. Blood samples were taken from 200 MS patients who were treated with interferon (100 responders and 100 non-responders). Using PCR-RFLP technique, the samples were subjected to enzymatic digestion with restriction enzymes ApaI, FokI, TaqI and BsmI. The data were evaluated using SPSS version 16, SNP Analyzer and Prism software, and K-tests and logistic regression.&#x0D; Results: A significant difference in the genotypic and allelic frequencies of ApaI (p=0.68), BsmI (p=0.65), FokI (p=0.57) and TaqI (p=0.50) polymorphisms in the patients between the two responsive and non-responsive groups to treatment was not observed.&#x0D; Conclusion According to our findings, there was no significant correlation between ApaI, FokI, TaqI and BsmI polymorphisms located in vitamin D receptor gene and response to treatment.

Vitamin D and Vitamin D Receptor Polymorphisms Relationship to Risk Level of Dental Caries

Dental caries is a multifactorial disease with multiple risk factors. Vitamin D levels (VDLs) and vitamin D receptor polymorphisms (VDRPs) have been investigated for this reason. The aim of this narrative review is to investigate the relation and the factors affecting vitamin D deficiency (VDD), VDRP, Early Childhood Caries (ECC) and Severe Early Childhood Caries (S-ECC) in children (primary and mixed dentition) and dental caries risk in adults (permanent dentition). Additionally, we present a model incorporating factors and interactions that address this relationship. Methods: Three databases (PubMed/MEDLINE, Web of Science, Cochrane Library) were comprehensively searched until 17 January 2023 using the following keywords: “vitamin D”, “vitamin D receptor polymorphism”, “dental caries”, and “dental caries risk”, finding 341 articles. Two reviewers searched, screened, and extracted information from the selected articles. All pooled analyses were based on random-effects models. Eligibility criteria were articles using dmft/DMFT diagnostic criteria with calibrated examiners, probability sampling, and sample sizes. We excluded studies conducted on institutionalized patients. A total of 32 studies were finally used. Results: In most studies, TaqI, FokI, and BsmI polymorphisms affected the prevalence of dental caries. A strong correlation between ECC, S-ECC, and the prevalence of dental caries was reported in association with VDD and maternal intake of VD in primary dentition. Regarding the influence in mixed dentition, the results were found to be inconclusive. A slight positive influence was reported for permanent dentition. Conclusions: Factors affecting caries risk were maternal intake, socioeconomic factors, and level of VD. There is a certain need for more well-conducted studies that will investigate the association between VDR gene polymorphisms and the prevalence of dental caries in mixed and permanent dentition, specifically in adult patients.

The relations of vitamin D receptor gene polymorphisms with risk of obesity, metabolic syndrome, hepatostetosis in Turkish children

Purpose: The aim of study was to determine the relation of vitamin D receptor gene (VDR) polymorphisms of TaqI (rs731236), ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810) with the risk of obesity, metabolic syndrome and hepatosteatosis in children.Materials and methods: 130 obese and 130 healthy children of age range between 10-16 years included in this study. Anthropometric measurements, biochemical evaluations and abdominal USG of all children were done. Obese and healty children were analyzed for the most common polymorphisms of the VDR gene by restriction fragment length polymorphism’s technique. The diagnosis of metabolic syndrome was made using the International Diabetes Federation criteria.Results: Genotypic distribution of BsmI, FokI, and TaqI polymorphism were found statistically different between obese patients and control group, but genotypic distribution of all studied polymorphisms were not found statistically different in obese patients with metabolic syndrome or hepatosteotosis. Conclusion: BsmI polymorphism (rs1544410) was found to have a significant positive effect on the development of obesity, metabolic syndrome and hepatosteatosis. Children who carry risk factors for childhood obesity could be screened before the development of obesity and associated metabolic complications using the BsmI polymorphism of the VDR gene.

VITAMIN D RECEPTOR GENE APAI AND TAQI POLYMORPHISM IN PATIENTS WITH TYPE II DIABETES MELLITUS USING PCR-RFLP METHOD IN KURDISTAN REGION

Background: Type 2 diabetes mellitus that characterized by insulin resistance and it is a risk of many diseases the impact of genetic factors on diabetes is well documented. Vitamin D receptor (VDR) gene polymorphisms have been linked to T2DM. In this study, we analyzed the relation between TaqI and ApaI VDR gene polymorphisms and T2DM subjects by using the PCR-RFLP method in Kurdish patients.

Serum vitamin D levels and vitamin D receptor gene ApaI and TaqI polymorphisms in patients with morphea: a case-control study.

A uncommon inflammatory condition called morphea causes fibrosis in the skin and subcutaneous tissue. The key stages in the pathophysiology are vascular damage, immunological response, and fibrosis. Numerous research have examined the relationships between the immune system, fibrosis, and vitamin D, but the exact pathogenetic pathways of morphea remain poorly understood. The purpose of this study was to investigate serum 25(OH)D levels and the ApaI (rs7975232) and TaqI (rs731236) polymorphisms of the vitamin D receptor (VDR) in morphea patients. There were 48 age- and sex-matched controls and 41 morphea patients total. VDR polymorphisms were found using PCR tests and gel electrophoresis, and serum 25(OH)D levels were determined using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). The patient group consisted of 37 females (90.2%) and 4 males (9.8%). The patients' mean age was 38.68 ± 17.54years. In terms of VDR ApaI and TaqI polymorphisms, there was no discernible difference between the patient and control groups. TaqI polymorphism heterozygosity was discovered in all patients with progressive disease, and this finding was statistically significant (p = 0.012). Patients' mean serum 25(OH)D levels were 16.98 ± 11.55ng/mL, while those in the control group were 18.02 ± 14.30ng/mL. VDR polymorphisms, vitamin D levels, disease subtype, age of onset, and responsiveness to treatment did not significantly correlate. In our research, we discovered that TaqI polymorphism may be related to the severity of the disease and that the polymorphisms of the VDR ApaI and TaqI were not associated with morphea susceptibility.

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

BackgroundThe 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.MethodsBlood 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.ResultsTaqI 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.ConclusionAssociation of BsmI genotypes with the incidence of CAD revealed that the genetic variation of VDR might play a role in the pathogenesis of CAD.

Vitamin D Receptor Polymorphisms Among the Turkish Population are Associated with Multiple Sclerosis.

Multiple sclerosis (MS) is an inflammatory disease characterized by demyelination and axonal degeneration affecting the central nervous system. Among the genetic factors suggested to be associated with this disease are polymorphisms to the vitamin D receptor (VDR) gene. We tested the hypothesis that polymorphisms in the vitamin D receptor (VDR) gene are associated with MS. The aim of the study was to investigate the relationship of MS with the VDR gene Fok-I, Bsm-I and Taq-I polymorphisms among the Turkish population. This study contains 271 MS patients and 203 healthy controls. Genomic DNA was isolated from the samples and the VDR gene Fok-I, Bsm-I and Taq-I polymorphism regions were amplified by polymerase chain reaction (PCR). The PCR products were digested, and the genotypes were determined based on size of digested PCR products. Our results demonstrate associations between MS and the distribution of the VDR gene Fok-I T/T polymorphism genotype in a dominant model, VDR gene Fok-I T allele frequency, distribution of VDR gene Taq-I C/C polymorphism genotype in a dominant model and VDR gene Taq-I C allele frequency (Pearson test, p<0.05). However, there was no association between MS and the VDR gene Bsm-I polymorphisms for the genotype distribution (Pearson test, p>0.05) or allele frequency (Pearson test, p>0.05). Fok-I and Taq-I VDR gene polymorphisms are significantly associated with MS in dominant, homozygote and heterozygote inheritance models among the Turkish population.

Bariatric Surgery and Vitamin D: Trends in Older Women and Association with Clinical Features and VDR Gene Polymorphisms.

(1) Background: Obesity and its comorbidities can cause burdens and limitations. Bariatric surgery (BS) is indicated as a safe procedure to reduce body mass and improve present comorbidities. However, several complications were reported, such as vitamin D [25(OH)D] deficiency. We evaluated if 25(OH)D serum levels relate to clinical characteristics, symptoms, or habits in women after their BS, and whether the vitamin D receptor (VDR) gene's TaqI and FokI polymorphisms affected 25(OH)D levels and the total body bone mineral density (TBBMD). (2) Methods: This cohort cross-sectional comparative analytical prospective study consisted of 27 women, 61.6 ± 5.0 years, submitted to BS one year prior at a public reference hospital, DF-Brazil. All participants were asked to follow the physical and dietary activity recommendations and received vitamin D3 supplements. Their anthropometric, biochemical, and immunological measurements and blood samples were obtained. (3) Results: 73.3% of participants had low 25(OH)D levels, and their levels correlated positively with TBBMD and negatively with systolic pressure. VDR TaqI did not affect 25(OH)D levels, whereas VDR FokI's allele f presence correlated to a median rise in 25(OH)D levels. Neither polymorphism correlated to TBBMD. (4) Conclusions: 25(OH)D levels were positively correlated with TBBMD, negatively with systolic blood pressure, and were higher in those with the VDR FokI allele f.

Genetic Association of VDR gene Apa1 and Taq1 Variants with Scleroderma in an Iranian Northeast Population.

Despite vigorous research efforts, the etiology of scleroderma (systemic sclerosis (SSc)) remains still unclear and both genetic and environmental factors clearly contribute to the pathogenesis of scleroderma. Reports of aberrant vitamin D status in scleroderma patients suggest a need for considering the genotype and allele frequencies of VDR gene polymorphisms. This case-control study aimed to investigate the possible association of two common polymorphisms of the VDR gene (ApaI, and TaqI) with susceptibility to scleroderma in an Iranian population. Using polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP), ApaI and TaqI polymorphisms in the VDR region were genotyped in 51 patients with scleroderma and 50 healthy controls. Logistic regression analysis was performed to calculate the genotypes odds ratios (ORs) as a measure of association with the presence of scleroderma. Haplotype and linkage disequilibrium analyses were also performed on the detected genotypes. No significant differences were found for the allelic and genotype distributions of ApaI and TaqI polymorphisms between patients with scleroderma and healthy controls (p>0.05). In haplotype analysis, three haplotypes TA, CA, and TC, with a frequency greater than 1% were identified. However, none of them was associated with the risk of scleroderma. Our preliminary study showed no evidence of an association between ApaI and TaqI polymorphisms and scleroderma. As the association between VDR polymorphisms and autoimmune diseases varies across the different ethnic populations, further large cohort studies are necessary to confirm the results.

Associations of vitamin D receptor encoding gene variants with premenopausal breast cancer risk.

This study evaluates whether vitamin D receptor (VDR) gene variations are associated with premenopausal breast cancer in Pakistani cohorts. Genomic DNA was isolated from 228 breast cancer patients and 500 non-cancer controls. Six polymorphic variants (rs11568820, rs4516035, rs2228570, rs1544410, rs7975232, rs731236) of the VDR gene were genotyped using PCR-RFLP analysis. All statistical analysis was carried out on IBM-SPSS 23 at p-value <.05. Chi-square test and odds ratios (ORs) along with 95% confidence interval (CIs) were applied to evaluate the relationship between VDR gene polymorphisms and breast cancer. Results showed that the A/A genotype of EcoRV (OR=2.125, 95% CI=1.024 to 4.412) and the A/a genotype of Apa1 (OR=6.094, 95%CI=4.111 to 9.033) gene polymorphism had an increased risk of premenopausal breast cancer. No associations of the Bsm1 and Taq1 polymorphisms were observed in premenopausal women. Moreover, the Cdx2 GG (OR=0.34, 95%CI=0.192-0.602) genotype had a significant protective effect on breast cancer. However, strong LD was existed between Bsm1/Taq1 (D'=0.757, CI=0.67-0.82) and Apa1/Taq1 (D'=0.695, CI=0.6-0.77). Haplotype analysis showed no association between premenopausal breast cancer and VDR haplotypes. These analyses indicates that the VDR EcoRV A/A and Apa1 A/a genotypes may be risk factors for breast cancer development among premenopausal women.

Vitamin D Receptor Gene Polymorphisms Affect Osteoporosis-Related Traits and Response to Antiresorptive Therapy.

The present study analyzed the effect of vitamin D receptor (VDR) gene polymorphisms (ApaI, TaqI, BsmI, FokI, and Cdx2) on bone mineral density (BMD), biochemical parameters and bone turnover markers, fracture prevalence, and response to three types of antiresorptive therapy (estrogen-progesterone, raloxifene, and ibandronate) in 356 postmenopausal women from Slovakia. Association analysis revealed a significant effect of BsmI polymorphism on lumbar spine BMD, serum osteocalcin (OC), and β-CrossLaps levels. While ApaI and Cdx2 polymorphisms were associated with OC and alkaline phosphatase, TaqI polymorphism affected all turnover markers. ApaI, TaqI, and BsmI genotypes increased the risk of spinal, radial, or total fractures with odds ratios ranging from 2.03 to 3.17. Each of therapy types evaluated had a beneficial effect on all osteoporosis-related traits; however, the VDR gene affected only ibandronate and raloxifene treatment. ApaI/aa, TaqI/TT, and BsmI/bb genotypes showed a weaker or no response to ibandronate therapy in femoral and spinal BMD. The impact of aforementioned polymorphisms on turnover markers was also genotype dependent. On the contrary, only TaqI and BsmI polymorphisms influenced raloxifene therapy, even only in lumbar spine BMD. These results point to the potential of using the VDR gene in personalized pharmacotherapy of osteoporosis.

Association of vitamin D receptor polymorphisms with colorectal cancer susceptibility: A systematic meta-analysis

Recent studies have reported an association between vitamin D receptor (VDR) polymorphisms and colorectal cancer (CRC) risk; however, the results are controversial. This meta-analysis was performed to investigate whether the Cdx-2, Tru9I, FokI, BsmI, TaqI, and ApaI polymorphisms were correlated with CRC susceptibility. All potential studies were retrieved by searching the PubMed, EMBASE, and Cochrane Library databases through October 2, 2021. Odds ratios (ORs) with 95% confidence intervals were used to evaluate the correlation between VDR gene Cdx-2, Tru9I, FokI, BsmI, TaqI, and ApaI polymorphisms and CRC risk. In this meta-analysis, the BsmI variant was significantly correlated with a lower risk of CRC, especially in Caucasian population (B vs b: OR 0.94, 95%CI 0.90-0.99; BB vs bb: OR 0.88; 95%CI 0.79-0.97; BB vs Bb/bb: BB vs Bb/bb: OR 0.89; 95%CI 0.81-0.98). A statistically significant result from the FokI polymorphism was observed in colon cancer rather than rectal cancer (Ff vs FF: OR 0.86, 95%CI 0.84-0.93; ff/Ff vs FF: OR 0.88, 95%CI 0.79-0.98; ff vs Ff/FF: OR 0.90, 95%CI 0.82-0.99). Similarly, Cdx-2 polymorphism was found to be associated with decreased CRC risk among Africans (C vs c: OR 0.50, 95%CI 0.33-0.75; CC vs cc: OR 0.09, 95%CI 0.01-0.77; Cc vs cc: OR 0.49, 95%CI 0.30-0.81; CC/Cc vs cc: OR 0.45, 95%CI 0.28-0.74,). Our findings indicate that VDR polymorphisms are significantly associated with CRC risk.

The Taq 1 polymorphism of Vitamin D receptor gene is associated with oral cancer and preoral cancer in North Indian population.

Oral cancer is known as one of the most common cancers, with a poor prognosis, related to delayed clinical diagnosis, either due to the lack of particular biomarkers related to the disease or costly therapeutic alternatives. In this study association of single nucleotide polymorphism (Taq1, T>C) in Vitamin D receptor gene with oral cancer and pre oral cancer was studied. Total 230 patients of precancerous oral lesions (Leukoplakia 70, Oral Sub mucous fibrosis 90, Lichen Planus 70), 72 oral cancer patients and 300 healthy control subjects were genotyped by PCR-RFLP methods. Chi-square test was used for calculation of genotype and allele frequencies. Mutant genotype CC as well as C allele were found to significantly decrease the risk of oral disease (P value=0.04, OR=0.60 and P value=0.02, OR=0.75 respectively). In particular, compared to non smokers, smokers with TC & CC genotypes were at decrease risk of oral diseases (P value=0.0001, OR=0.04). The mutant allele genotype CC as well as the mutant allele C showed protective association with leukoplakia (P value=0.01, OR=0.39 & P value=0.009, OR=0.59 respectively). However, individual with CC genotype had developed high cell differentiated grade at diagnosis (OR= 3.78, P value= 0.008). This study concludes that VDR (Taq1) polymorphism is associated with oral cancer and pre oral cancer susceptibility in North Indian population.