Vitamin D Receptor Genetic Polymorphisms Research Articles

Vitamin D Supplementation and Genetic Polymorphisms Impact on Weight Loss Diet Outcomes in Caucasians: A Randomized Double-Blind Placebo-Controlled Clinical Study.

Vitamin D deficiency or insufficiency is common in obese people, with some studies suggesting that low vitamin D level might be an independent predictor of obesity. Thus, the purpose of the present randomized, double-blind, placebo-controlled study was to investigate the effect of oral spray vitamin D3 3000 IU supplementation along with personalized weight-loss diet on obesity markers in overweight and obese Caucasians with vitamin d deficiency or insufficiency. The impact of vitamin D receptor (VDR) and adrenergic receptors (ADRs) genetic variants on vitamin D levels and weight loss diet outcomes was also investigated. After signing informed consent, a total of 125 eligible volunteers were randomly assigned into vitamin D (vitamin D3 3000 IU/d oral spray supplementation, n = 76) or placebo (xylitol, water, mint, n = 49) group following a weight loss program (600 calories less than the total energy expenditure of each volunteer) for 3 months. Fat mass, BMI, REE and 25(OH)D serum level were monitored on baseline and each month. DNA samples were extracted from buccal swabs and genotyped for the rs2228570 (VDR), rs1544410 (VDR), rs731236 (VDR), rs1800544 (ADRA2A), rs1801252 (ADRB1), rs1042713 (ADRB2), and rs4994 (ADRB3) polymorphisms. Statistical analysis was performed using SPSS package (v.23). Between group comparisons revealed significant improvement in serum 25(OH)D level and greater reduction in weight, BMI and fat percentage in the vitamin D group compared to placebo group (p < 0.05). In the vitamin D group, carriers of the rs2228570 T allele tended to have greater vitamin D level improvement compared with the homozygous C allele (p = 0.067). Furthermore, heterozygous (CT) for the rs731236 tended to have lesser weight loss (p = 0.068) and for the rs1042713, a lower decline in fat percentage was observed for homozygous AA carriers compared to the heterozygous (p = 0.051). In the control group, differences in weight loss (p = 0.055) and BMI (p = 0.045) were observed between rs1544410 AA and GG homozygous. In conclusion, vitamin D oral spray supplementation seems to improve vitamin D status and decrease obesity markers during a weight-loss intervention in overweight/obese Caucasians with vitamin D deficiency or insufficiency. Also, the results of the present study indicate that VDR and ADRs genetic polymorphisms seem to influence vitamin D supplementation response and obesity markers.

Vitamin D receptor rs2228570 and rs1544410 genetic polymorphisms frequency in Iraqi thalassemia patients compared to other ethnic populations

BackgroundThe genetic polymorphisms of vitamin D receptor (VDR) have an association with thalassemia development, additionally to the environmental elements that elicited the disorder in the genetically predisposed individuals. As well, VDR functions responsible for the regulation of bone metabolism, such its part in immunity. AimThe sitting study intended to inspect the association between thalassemia disease and the genetic polymorphisms of VDR among the Iraqi population then compared these findings to other findings of thalassemia patients in other different ethnic populations. Materials and methodsThe restriction enzymes Bsm-I and Fok-I were applied to determine the genetic polymorphisms frequencies of VDR by a Polymerase Chain Reaction – Random Fragment Length Polymorphisms (PCR-RFLP) techniques of the targeted parts (rs2228570 and rs1544410) in 70 Iraqi patients suffering from thalassemia (18 males and 52 females) and 75 Iraqi healthy participants as a control group (18 males and 52 females). Also, the comparison between the present findings of VDR genetic polymorphisms in Iraqi thalassemia patients and other previous findings for thalassemia patients in different ethnic populations for the selected VDR Bsm-I and Fok-I sites were done. ResultsThe present findings manifested a significant difference of VDR Bsm-I and Fok-I genetic polymorphisms frequency (rs2228570 and rs1544410) in the thalassemia patient's group contrasted to the healthy control group. In VDR rs2228570, the AA genotype and A allele frequency were significantly increased in the patients' group contrasted to the healthy control group (44.29 vs. 8.0%, OR: 9.14, 95% CI: 3.53–23.68, p: 4.1 × 10−7; 69.0 vs. 27.0%, OR: 6.02, 95% CI: 3.27–11.06, p: 3.9 × 10−9, respectively). while, the results of VDR genetic polymorphisms rs1544410 manifested that the CC and CT genotyping and C allele frequency were significantly increased among the patient's group contrasted to the healthy control group (28.75 vs. 6.67%, OR: 5.60, 95% CI: 1.98–15.81, p: 7.2 × 10−4; 57.14 vs. 24.0, OR: 4.22, 95% CI: 2.08–8.55, p: 8.1 × 10−5; and 57.0 vs. 19.0%, OR: 6.39, 95% CI: 3.0–10.66, p: 3.9 × 10−9, respectively). Also, it manifested the genetic polymorphisms variance of VDR rs2228570 and rs1544410 between the Iraqi thalassemia patients and other ethnic thalassemia patients. The results showed different variants among the Iraqi thalassemia patients' polymorphisms and other ethnic thalassemia patients' polymorphisms. ConclusionsThe present results demonstrated a significant association between the genetic polymorphisms of VDR and thalassemia disease, the AA genotype and A allele frequency was significantly increased among the thalassemia patients' group compared to the controls in VDR Bsm-I polymorphism (rs2228570). While the CC and CT genotypes and C allele frequency were significantly increased among the thalassemia patients' group compared to the controls in VDR Fok-I polymorphism (rs1544410). As well, it indicates the variance of VDR Bsm-I and Fok-I genetic polymorphisms frequencies between the Iraqi thalassemia patients and other thalassemia patients from different ethnic populations.

Interactions Between Vitamin D and Calcium Intake, Vitamin D Receptor Genetic Polymorphisms, and Colorectal Cancer Risk.

Vitamin D has anticarcinogenic properties and acts through vitamin D receptor (VDR) to carry out its functions. This study explored the independent and combined effects of dietary vitamin D and calcium, and VDR genetic polymorphisms on colorectal cancer risk in a Chinese population. This ongoing case-control study recruited 488 cases with histologically confirmed colorectal cancer and 496 sex- and age-matched controls. Vitamin D and calcium intakes were assessed by a validated food frequency questionnaire, and VDR genotype was conducted for Fok I (rs2228570), Bsm I (rs1544410), Apa I (rs7975232), and Taq I (rs731236). Unconditional logistic regression was used to calculate odds ratio and 95% confidence interval after adjusting for various confounders. No significant association was found between Fok I, Bsm I, Apa I, Taq I, and colorectal cancer risk. Higher intakes of dietary vitamin D and calcium were associated with 47% and 50% reduction in colorectal cancer risk. Significant interaction was observed between dietary vitamin D intake and Apa I polymorphisms in relation to colorectal cancer risk (Pinteraction = 0.006). Subjects with higher dietary vitamin D intake and mutant Apa I A allele had a substantially decreased risk of colorectal cancer compared to Apa I aa carriers with lower vitamin D intake. Our study supports that Apa I may interact with dietary vitamin D intake on colorectal cancer risk. However, no interactions were found between dietary vitamin D or calcium intakes and Fok I, Bsm I, and Taq I in relation to colorectal cancer risk.

Effects of Vitamin D Receptor, Cytochrome P450 3A, and Cytochrome P450 Oxidoreductase Genetic Polymorphisms on the Pharmacokinetics of Remimazolam in Healthy Chinese Volunteers.

Remimazolam is a new ultra-short-acting benzodiazepine used to induce and maintain anesthesia and procedural sedation. Its compound structure is similar to midazolam's. Midazolam metabolism might be affected by vitamin D receptor (VDR), cytochrome P450 3A, and cytochrome P450 oxidoreductase genetic polymorphisms. This study investigated the effects of VDR, cytochrome P450 3A, and cytochrome P450 oxidoreductase genetic polymorphisms on the pharmacokinetics of remimazolam in healthy Chinese volunteers after a single intravenous injection of remimazolam besylate. Blood samples were collected from subjects (n = 62) at scheduled time intervals before and after injection. High-performance liquid chromatography-tandem mass spectrometrywas used to quantify plasma remimazolam and RF7054 (its inactive carboxylic acid metabolite) concentrations. The relationship between plasma remimazolam concentration, pharmacokinetic parameters, and polymorphic alleles was assessed for each subject. The rs4516035 allele affected the elimination half-life of RF7054 (P = .043), while the rs1544410 allele affected the dose-normalized maximum observed plasma concentration (Cmax /D) of remimazolam (P = .025) in 46 volunteers. Results showed that VDR genetic polymorphisms might affect the pharmacokinetics of remimazolam in the Chinese population.

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

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

Relationships between vitamin D receptor genetic polymorphisms and endometriosis in Korean women

Objectives: Vitamin D and vitamin D receptor (VDR) are closely associated with both various immune system functions and estrogen-related pathways. The authors hypothesized that VDR genetic polymorphisms are associated with endometriosis risk. In this casecontrol study, the authors investigated the associations between polymorphisms in the VDR gene (FokI, BsmI, ApaI, and TaqI) and endometriosis risk. Materials and Methods: This case-control study included 30 women with endometriosis and 30 women without endometriosis. Genotyping of VDR polymorphisms was conducted using polymerase chain reaction and DNA sequencing. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between the four VDR polymorphisms and endometriosis risk using Fisher’s exact test. Results: The four VDR genetic polymorphisms showed no significant associations with endometriosis risk. Similarly, a combination analysis indicated that no combinations of polymorphisms were associated with endometriosis risk. However, the present analysis combining three polymorphisms revealed very low ORs (CGGT: 0.536, TGTT: 0.250, and CGTT: 0.321). Conclusion: The present results suggest that VDR polymorphisms do not affect endometriosis risk in Korean women. However, the genotype frequencies of ApaI and TaqI differed between endometriosis patients and controls. Therefore, it is necessary to further validate the relationship between VDR polymorphisms and endometriosis risk in large-scale samples.

New evidence for associations between vitamin D receptor polymorphism and obesity: case-control and family-based studies.

Association between vitamin D receptor (VDR) genetic polymorphism and obesity was observed in several case-control studies. This study hypothesized that these associations could be verified in family-based study. We aimed at investigating the associations between VDR SNPs and obesity (BMI ≥ 28 kg/m2) by case-control study with 688 subjects and family-based study with 419 pedigrees. The results of case-control study suggested that rs3847987 (AC vs CC, Adjusted OR: 1.938, 95% CI: 1.359-2.763, P = 0.000405) was associated with obesity. Allele C of rs3847987 was risk factors for obesity (P = 0.006). Furthermore, association of rs3847987 with BMI was verified in family-based study (Z = 2.077, P = 0.037811). In addition, sibling with AC genotype of rs3847987 had significant higher BMI than CC genotype in the same family (P = 0.03). Therefore, it could be concluded that VDR genetic polymorphism (rs3847987) may be associated with obesity.

Association of Vitamin D Receptor Gene Polymorphism with Metabolic Syndrome and Type 2 Diabetes Mellitus in a Sample of Egyptian Patients

Background. There are insufficient data on the association of vitamin D receptor (VDR) genes polymorphism and type 2 diabetes mellitus (type 2 DM), and various components of metabolic syndrome among Egyptian patients. The aim of the present study was to study the association of different SNPs of VDR genes BsmI, ApaI, TaqI and FokI and components of metabolic syndrome and type 2 DM among cohort of Egyptian patients. Methods. The study is a case-control study. Patients included in the study were divided into three groups. Group 1 included 78 patients with type 2 DM; group 2 included 72 patients with metabolic syndrome and one hundred age-matched healthy subjects were served as control group. Full biochemical study and serum 25 hydroxy vitamin D (25(OH)D) were done. Purified DNA was subjected to study with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for genotyping of SNPs of VDR gene. Data were presented as mean and standard deviation, and were analysed as appropriate by using the one-way ANOVA or paired t-test. Pearson correlation coefficient was used to correlate between variables. Results. Study of VDR genetic polymorphism had shown significant increase in the prevalence of Ff genotypes among diabetic patients and patients with manifestations of metabolic syndrome. There was significant negative correlation between 25(OH)D and total cholesterol, triglyceride, fasting and post-prandial blood glucose levels, waist circumference and diastolic blood pressure. Conclusion. The genetic polymorphism of VDR might play a role in the pathophysiology of type 2 DM and metabolic syndrome., however, more longitudinal studies are still required to support these finding.

Role of vitamin D receptor (VDR) genetic polymorphism in onset of type 2 diabetes mellitus: A Review

Numerous studies disclosed the independent role of VDR genetic polymorphisms involved in pathogenesies of various metabolic disorders like type 2 diabetes mellitus in different populations, however no any conclusive or even key study conducted on South Asian population especially Pakistani population except on Indian population. Worldwidle, vitamin D defeciency and type 2 diabetes mellitus (T2DM) are two interlated and most common health problems. Such interlationship is involved complex inheritance pattern.The polymorphisms of various genes including vitamin D receptor (VDR) might affect genetic susceptibility of T2DM by developing malfunctioning of beta pancreatic cells or insulin resistance. Genetic architecture of T2DM is different among various ethnic populations. The present review will focus on concept that polymorphism of VDR gene may has role in susceptibilty of onset of T2DM and its pathogenesises.

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

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

Vitamin D Status and Association of VDR Genetic Polymorphism to Risk of Breast Cancer in Ethiopia.

Emerging evidence associates vitamin D deficiency and vitamin D receptor (VDR) genetic variations with risk for breast cancer. This study investigated the prevalence of vitamin D deficiency and its association with tumor characteristics and the implications of VDR genetic variations for risk of breast cancer in Ethiopia. This unmatched case–control study involved 392 female breast cancer patients and 193 controls. The plasma 25-hydroxyvitamin D (25(OH)D3) level was quantified in chemotherapy-naïve (N = 112) and tamoxifen-treated patients (N = 89). Genotyping for the VDR common variant alleles rs7975232 (ApaI), rs2228570 (FokI), and rs731236 (TaqI) was done. Eighty-six percent of the patients were vitamin D deficient (<50 nmol/L). Chemotherapy-naïve breast cancer patients had a higher prevalence of vitamin D deficiency (91.9% vs. 78.3%) compared to the tamoxifen-treated group (p < 0.001). The prevalence of severe vitamin D deficiency (<25 nmol/L) was significantly higher in chemotherapy-naïve (41.1%) than tamoxifen-treated (11.2%) patients. Vitamin D deficiency was not significantly associated with tumor characteristics or VDR genotype. The rs2228570 GG genotype was associated with increased risk of breast cancer (OR = 1.44, 95% confidence interval = 1.01−2.06). Our result indicates that rs2228570 might be a moderate risk factor for breast cancer development in the Ethiopian population. The high prevalence of severe vitamin D deficiency in treatment-naïve breast cancer patients indicates the need for nutritional supplementation of vitamin D at the time of chemotherapy initiation.

Impact of vitamin D receptor and binding protein gene polymorphisms in clinical and laboratory data of HCV patients: Cross sectional study.

Potential relationship of vitamin D, vitamin D receptor (VDR), and vitamin D binding protein (DBP) have been suggested in the pathophysiology of hepatitis C virus (HCV) infection. The aim of this observational study is to determine vitamin D levels, and VDR and DBP genetic polymorphism according demographic and laboratory data in chronic HCV patients (CHC).A total of 148 CHC patients gave serum samples for testing 25-hydroxyvitamin D (25 (OH)D) level by immunochemiluminometric assay (<20 ng/mL defined as deficient) and donated blood samples to allelic discrimination analysis using TaqMan assays. Analyzed single nucleotide polymorphisms (SNPs) were: VDR-rs7975232 (ApaI) C>A, rs731236 A>G (TaqI), rs1544410 C>T (BsmI), rs10735810 T>C (FokI) and carrier globulin/binding protein (GC)-rs4588 and rs7041 and the haplotype bAt [CCA]. Hepatic fibrosis was assessed using Fib-4 and Forns index.Eighty-two (54.40%) patients demonstrated deficiency of vitamin D and this was associated to AST (P = .019 [CI: 1.003–1.034]), total cholesterol (P = .038 [CI: 1.004–1.164]), fibrosis grade (P < .001 [CI: 0.000–0.844]), and FokI (P = .028) allele T presence. Association was found between VDR polymorphism and fibrosis (BsmI andTaqI), triglycerides (TaqI), and HDL (FokI). DBP polymorphism was associated to HCV genotype (GC rs7041), previous HCV treatment, and GGT (GC rs4588).In conclusion, low frequency of vitamin D deficiency was found, but VDR polymorphisms were frequently associated to fibrosis grade suggesting that they could be used as disease evaluation markers to understand the mechanisms underlying the virus–host interaction.

Vitamin D receptor polymorphisms and related biochemical parameters in various cancer species

Abstract Objective Certain cancer types have been shown to be associated with vitamin D deficiency. The aim of this study was to appraise the relationship between the vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) of VDR Fok1 and Bsm1 with serum vitamin D, calcium and phosphorus levels among patients of lung, colon, breast and pancreatic cancer patients. Materials and methods Groups; lung, colon, breast and pancreatic cancer patients (n=212) and 58 age-matched healthy controls. Serum levels of vitamin D were measured by immunochemiluminesence method and Fok1 and Bsm1 genotypes were assessed with Real-Time Polymerase Chain Reaction. Results VDR Fok1 and Bsm1 genetic polymorphisms have a significant difference between lung cancer and control group subjects (p=0.042, p=0.040, respectively). VDR Bsm1 genetic polymorphism has a significant association between breast cancer and control group according to the logistic regression model (p=0.038). Vitamin D levels were found significantly lower in all cancer groups (p&lt;0.01). Phosphorus levels of lung cancer and calcium levels of pancreatic cancer patients were statistically significantly lower than control group (p&lt;0.02, p&lt;0.01). Conclusion This study indicates that VDR genetic polymorphisms, calcium, phosphorus and vitamin D status of individuals were associated with certain cancer species.

Lead-Related Genetic Loci, Cumulative Lead Exposure and Incident Coronary Heart Disease: The Normative Aging Study.

BackgroundCumulative exposure to lead is associated with cardiovascular outcomes. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD), hemochromatosis (HFE), heme oxygenase-1 (HMOX1), vitamin D receptor (VDR), glutathione S-transferase (GST) supergene family (GSTP1, GSTT1, GSTM1), apolipoprotein E (APOE),angiotensin II receptor-1 (AGTR1) and angiotensinogen (AGT) genes, are believed to alter toxicokinetics and/or toxicodynamics of lead.ObjectivesWe assessed possible effect modification by genetic polymorphisms in ALAD, HFE, HMOX1, VDR, GSTP1, GSTT1, GSTM1, APOE, AGTR1 and AGT individually and as the genetic risk score (GRS) on the association between cumulative lead exposure and incident coronary heart disease (CHD) events.MethodsWe used K-shell-X-ray fluorescence to measure bone lead levels. GRS was calculated on the basis of 22 lead-related loci. We constructed Cox proportional hazard models to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CHD. We applied inverse probability weighting to account for potential selection bias due to recruitment into the bone lead sub-study.ResultsSignificant effect modification was found by VDR, HMOX1, GSTP1, APOE, and AGT genetic polymorphisms when evaluated individually. Further, the bone lead-CHD associations became larger as GRS increases. After adjusting for potential confounders, a HR of CHD was 2.27 (95%CI: 1.50–3.42) with 2-fold increase in patella lead levels, among participants in the top tertile of GRS. We also detected an increasing trend in HRs across tertiles of GRS (p-trend = 0.0063).ConclusionsOur findings suggest that lead-related loci as a whole may play an important role in susceptibility to lead-related CHD risk. These findings need to be validated in a separate cohort containing bone lead, lead-related genetic loci and incident CHD data.

The Associations Between the Polymorphisms of Vitamin D Receptor and Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Vitamin D receptor (VDR) polymorphisms were indicated to be associated with coronary artery disease (CAD); however, published studies reported inconsistent results.The aim of this meta-analysis is to reach a more accurate estimation of the relationship between VDR genetic polymorphisms and CAD risk.Eligible studies were retrieved by searching PubMed, Embase, VIP, Wanfang and China National Knowledge Infrastructure databases. Included and excluded criteria were formulated. The case group was patients with CAD, and the control group was healthy subjects. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate VDR polymorphisms associations with CAD risk. Heterogeneity was evaluated by Q statistic and I2 statistic.Seven studies of a total of 2306 CAD patients and 4151 control subjects met the inclusion criteria. The pooled results from Taq1 showed increased risk in allelic model (OR = 1.14, 95% CI = 1.02–1.28), dominant model (OR = 1.21, 95% CI = 1.02–1.43), heterozygote model (OR = 1.19, 95% CI = 1.00–1.1.42), and homozygote model (OR = 1.27, 95% CI = 1.01–1.61). Besides, Fok1 T > C showed decreased risk in allelic model (OR = 0.81, 95% CI = 0.65–1.00) and Fok1 A > G also showed decreased risk in allelic model (OR = 0.67, 95% CI = 0.45–1.00) and recessive model (OR = 0.55, 95% CI = 0.31–0.97). In Caucasian subgroup, Bsm1showed increased risk in allelic model (OR = 1.23, 95% CI = 1.02–1.47), heterozygote model (OR = 1.20, 95% CI = 1.00–1.44), and homozygote model (OR = 1.22, 95% CI = 1.02–1.45). In CAD patients with type 2 diabetes mellitus (T2DM), Apa1showed a decreased risk in heterozygote model (OR = 0.80, 95% CI = 0.66–0.98); however, increased risk in recessive model (OR = 5.00, 95% CI = 2.74–9.13) was discovered in CAD patients without T2DM.The Fok1 polymorphism may play a protective role in CAD, and the possible protective role in Apa1 CA genotype in CAD patients with T2DM needs further studies. The Taq1 polymorphism is found to be associated with a significant increase in CAD risk based on our analysis; moreover, increased risk in Apa1 polymorphism in CAD patients without T2DM and Bsm1 polymorphism in Caucasian group is also detected.

Vitamin D level and vitamin D receptor genetic variations contribute to HCV infection susceptibility and chronicity in a Chinese population

Vitamin D and vitamin D receptor (VDR) are involved in multiple immune-mediated disorders including chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the association between plasma vitamin D level, VDR genetic polymorphisms and risk of HCV infection susceptibility and chronicity. Seven single nucleotide polymorphisms (SNPs) in VDR gene were genotyped and plasma 25-hydroxyvitamin D [25(OH)D] levels were measured in a Han Chinese population of 898 HCV persistent infection cases, 558 spontaneous clearance subjects and 1136 uninfected controls with high risk of HCV infection. In this case–control study, the average plasma 25(OH)D level in persistent infection patients was significantly lower than that in spontaneous clearance cases (P=0.039) and controls (P=0.005). Logistic analyses indicated that rs7975232-C, rs2239185-T and rs11574129-T alleles were significantly associated with a decreased risk of HCV infection susceptibility (all PBonferroni<0.05, in additive/dominant models; Ptrend=9.000×10−4, combined effects in a locus-dosage manner). The protective effects of three favorable alleles were more evident among males, females and subjects aged ≤50years (all P<0.05). Haplotype analyses suggested that compared with the most frequent haplotype Ars7975232Trs731236Crs11574129, CTT was correlated with a reduced risk of HCV infection susceptibility (P=2.200×10−3). These findings implied that low vitamin D levels might be associated with an increased risk for HCV infection and chronicity, and favorable VDR variants (rs7975232-C, rs2239185-T and rs11574129-T) might contribute to a decreased susceptibility to HCV infection in a high-risk Chinese population.

The genetic polymorphisms in vitamin D receptor and the risk of type 2 diabetes mellitus: an updated meta-analysis.

Vitamin D receptor (VDR) genetic polymorphisms are considered to be associated with type 2 diabetes mellitus (T2DM), but this is inconclusive. The aim of this study is to quantify the association between polymorphisms of BsmI and FokI in the VDR gene and T2DM risk through literature review. Original articles published from 1999 to June 2014 were discovered through PubMed, ISI Web of Science, China National Knowledge Infrastructure, Chinese Wanfang Database, and the Chinese Biomedical Literature Database. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with software STATA version 12.0. Twenty-three articles containing 30 case-control studies were included. The association between the BsmI polymorphism and T2DM was weak in two genetic models (Bb vs bb and BB+Bb vs bb). The subgroup analysis showed that this association was only found in the studies with a small sample size (<200). A strong association between FokI polymorphism and T2DM indicated that this gene polymorphism was possibly a risk factor for T2DM (ff vs FF: OR=1.57, 95% CI: 1.28-1.93, p<0.001; Ff vs FF: OR=1.54, 95% CI: 1.31-1.81, p<0.001; ff+Ff vs FF: OR=1.57, 95% CI: 1.35-1.83, p<0.001), especially in Chinese populations. More reliable conclusions about associations between VDR genetic polymorphisms and T2DM will depend on studies with larger sample size and by ethnicity.

Effect modification by vitamin D receptor genetic polymorphisms in the association between cumulative lead exposure and pulse pressure: a longitudinal study.

BackgroundAlthough the association between lead and cardiovascular disease is well established, potential mechanisms are still poorly understood. Calcium metabolism plays a role in lead toxicity and thus, vitamin D receptor (VDR) polymorphisms have been suggested to modulate the association between lead and health outcomes. We investigated effect modification by VDR genetic polymorphisms in the association between cumulative lead exposure and pulse pressure, a marker of arterial stiffness.MethodsWe examined 727 participants (3,100 observations from follow-ups from 1991 to 2011) from the Normative Aging Study (NAS), a longitudinal study of aging. Tibia and patella bone lead levels were measured using K-x-ray fluorescence. Four single nucleotide polymorphisms (SNPs) in the VDR gene, Bsm1, Taq1, Apa1, and Fok1, were genotyped. Linear mixed effects models with random intercepts were implemented to take into account repeated measurements.ResultsAdjusting for potential confounders, pulse pressure was 2.5 mmHg (95% CI: 0.4-4.7) and 1.9 mmHg (95% CI: 0.1-3.8) greater per interquartile range (IQR) increase in tibia lead (15 μg/g) and patella lead (20 μg/g), respectively, in those with at least one minor frequency allele in Bsm1 compared with those with major frequency allele homozygotes. The observed interaction effect between bone lead and the Bsm1 genotype persists over time during the follow-up. Similar results were observed in effect modification by Taq1.ConclusionsThis study suggests that subjects with the minor frequency alleles of VDR Bsm1 or Taq1 may be more susceptible to cumulative lead exposure-related elevated pulse pressure.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-069X-14-5) contains supplementary material, which is available to authorized users.

Comment to "Vitamin D Receptor Poly(A) Microsatellite Polymorphism and 25-Hydroxyvitamin D Serum Levels: Association with Susceptibility to Breast Cancer".

To the Editor, The article by Colagar et al. [1], in the latest issue of this journal, showed the relationship between the genetic polymorphism of vitamin D receptor (VDR), as a VDR polyA allele L microsatellite variants, serum level of 25(OH)D3 and risk of breast cancer. As in many other type of malignancies, low levels of 25(OH)D3, the main circulating form of vitamin D following dietary intake, has been associated with higher breast cancer susceptibility, particularly with plasmatic levels of 25(OH)D3 below 20 to 32 ng/mL [2]. Therefore, one of the major goal pursued by physicians endeavoured to prevent or fight cancer is to increase plasma bioavailability of 25(OH)D3 by increasing vitamin D intake or ameliorating its gut adsorption, supplementation protocol or pharmacokinetics [3]. However, the paper by Colagar appears to raise the same concern that I addressed in some recent papers of mine [4], namely that the preventive effect of vitamin D on cancer depends on the wide collection of factors including genetic polymorphism for VDR [1], for example, for breast cancer the different ability of individuals to respond to 1,25(OH)2D3 might depend on the Taq1 VDR polymorphism [5]. The individual genetic endowment to respond to vitamin D, in such a fashion able to assess its presumptive chemopreventive potential against some important malignancies such as breast cancer, should be a fundamental hallmark to arrange any vitamin D supplementation protocol [4]. Other genetic polymorhisms may be involved in the chemopreventive role of 25(OH)D3, for example those ones regarding P450 family of cytochromes [6], as interestingly CYP1A1 is involved in xenobiotic metabolism and is a VDR target [7], moreover CYP3A4 is a human microsomal 25(OH)D3 hydrolase [8]. Because of the genetic variability of VDR exising within the Causasian population, the authors discussed the controversial issue that any variant in VDR may influence the activity of vitamin D against tumors and their prevalence in the population [1]. Yet, some correlation exists between low levels of circulating 25(OH)D3 and frequency of breast cancer [2,9], which should suggest for an increase in vitamin D intake as a supplementation aid, but very few reports correlated positive outcomes for breast cancer incidence following vitamin D supplementation [3,10]. While several papers associated cancer risk with a low 25(OH) D3 plasma level, the reason of this insufficient bioavalailability is far to be elucidated. Cancer cells can promote the 25(OH) D3 enzymatic hydroxylation, contribuiting in the reduction of the level in the circulating form [11,12], The protective effect against breast cancer claimed by the authors [1] might derive from a wide panoply of variability, which may even involve P450 cytochromes and aryl hydrocarbon receptor polymorphism [13,14], though some contradictory evidence yet exists [15]. The conclusion which the authors reached assessed that breast cancer risk is related to low levels of the circulating metabolite 25(OH)D3 and to a favorable assessment of a VDR genetic polymorphism, particularly with poly(A) long (LL+LS) microsatellite alleles [1]. Interestingly, this genetic polymorhism was associated with breast cancer also in a Northern Indian population, nearby the Iranian regions from which the authors recruited their patients [16]. Interestingly, Fok1 polymorphism is a poly(A) microsatellite polymorphism, which was recently closely associated to breast cancer [17], although yet Fok1 is also a VDR polymorphism that has been associated with many other types of cancers [18] and even with pulmonary tuberculosis susceptibility [19]. The authors did not clarify which kind of VDR polymorphism, previously described in the literature, they reported in their paper. The genetic association of VDR polymorphism to several types of cancer makes particularly puzzling the role of the genetic variability of vitamin D enzymes and receptors in the presumptive chemopreventive role of 1,25(OH)2D3. HLA-aplotype genetic linkage may be a possible path to focus onto vitamin D action on tumors. Due to the strong association with tuberculosis (TB) susceptibility and Fok1 VDR polymorphism [19], a suggestion might come from the evidence that some HLA alleles, such as the aplotypes HLA-DRB1, HLA-DQB1 or more precisely DRB1*1101-1121-DQB1*05 are associated with TB as well as the polymorphic SNP variants Fok1, Bsm1, Apa1, and Taq1, some of which related to breast cancer [20]. The question is if some HLA aplotypes in linkage disequilibrium with VDR polymorphic genes may be used as genetic markers to evaluate the individual's vitamin D response against breast cancer [21]. This issue puts questions and concerns about the fundamental role of genetic determinants for ensuring vitamin D efficacy in counteracting cancer malignancy through its immune modulating and hormonal action.

Vitamin D receptor genetic polymorphism is significantly associated with decreased risk of hypertension in a Chinese Han population.

The aim of this study was to investigate the association of vitamin D receptor (VDR) gene polymorphism and hypertension in a Chinese Han population. The authors genotyped 3 tagSNPs (rs11574129, rs2228570, and rs739837) of the VDR gene using TaqMan assays in a case-control study including 2409 patients with hypertension and 3063 controls. The results showed that rs2228570 presented statistical correlations with decreased risk of male hypertension after adjustment for confounding factors, odds ratios (ORs) and 95% confidence intervals (CIs) of additive, dominant, and recessive models were 0.828 (0.74-0.927), 0.75 (0.631-0.89), and 0.816 (0.67-0.995), and P values were .001, .001, and .044, respectively. Significant associations were found in the smoking population and ORs (95% CIs) of additive and dominant models were 0.81 (0.69-0.952) and 0.71 (0.552-0.913) (P values .011 and .008), respectively, after adjustment for covariates. Quantitative trait analysis indicated that the untreated cases with TT genotype of rs2228570 showed higher systolic blood pressure compared with the TC/CC genotype (P=.015). Our findings suggest that VDR genetic polymorphism rs2228570 is significantly associated with the decreased risk of hypertension in Chinese men and smokers.