Association between vitamin D plasma concentrations and VDR gene variants and the risk of premature birth.
Ontology highlight
ABSTRACT:
SUBMITTER: Dutra LV
PROVIDER: S-EPMC6938626 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Publications
Association between vitamin D plasma concentrations and VDR gene variants and the risk of premature birth.
Dutra Letícia Veríssimo LV Affonso-Kaufman Fernando Alves FA Cafeo Fernanda Ramires FR Kassai Milene Saori MS Barbosa Caio Parente CP Santos Figueiredo Francisco Winter FW Suano-Souza Fabíola Isabel FI Bianco Bianca B
BMC pregnancy and childbirth 20191231 1
<h4>Background</h4>Premature birth is the main cause of mortality in children under 1 year, and vitamin D deficiency during gestation is associated with prematurity. The effects of vitamin D are mediated by its receptor, which is encoded by the VDR gene. VDR variants-such as single nucleotide variation (SNV)-are associated with increased risk of prematurity, but there are conflicting results. We evaluated serum vitamin D concentrations and the frequency of TaqI/A > G, BsmI/C > T, ApaI/C > A, and ...[more]
Similar Datasets
Project description:AimThis study investigated the associations among early pregnancy vitamin D concentrations, seasonality, and vitamin D metabolic gene variants and how these variables related alone and in interaction with the risk of gestational diabetes mellitus (GDM).MethodsResearch participants were women from the Ma'anshan birth cohort study in China. The overall study included 3110 women to explore the association between early pregnancy vitamin D concentrations and the risk of GDM. In the current analysis, a nested case-control study of 274 GDM cases and 380 controls was conducted to investigate seven vitamin D metabolic gene variants and the risk of GDM. Vitamin D concentrations were measured by radioimmunoassay. Genotypes were determined by improved multiple ligase detection reaction. Interactions between genetic variants and vitamin D as predictors of the risk of GDM were evaluated by a pair-wise analysis under a multiplicative interaction model.ResultsVitamin D concentrations were not significantly associated with the risk of GDM (OR = 0.79, 95% CI = 0.55-1.13) after adjusting for seasonality. Fall-winter conceptions had a 37% decreased risk of GDM compared with spring-summer conceptions (OR = 0.63, 95% CI = 0.49-0.81), independent of vitamin D concentrations. Two VDR gene variants rs1544410 (OR = 2.03, 95% CI = 1.17-3.51 for CT versus CC) and rs731236 (OR = 2.42, 95% CI = 1.29-4.55 for GA versus AA) were significantly associated with the risk of GDM. No interactions among genetic variants and vitamin D concentrations were detected.ConclusionEarly pregnancy vitamin D insufficiency or deficiency was not significantly associated with the risk of GDM. The results of this study emphasize the importance of genetic variants in VDR and conception season as factors that affect the risk of GDM.
| S-EPMC6613005 | biostudies-literature
Project description:BackgroundVitamin D metabolism and obesity have been linked by several studies, however the reason for this association is unclear. Our objective was to investigate potential correlations between genetic variants in key enzymes of vitamin D metabolism and the body mass index on a representative and random sample of Hungarian adults.MethodsAltogether 462 severely vitamin D deficient individuals were studied at the end of winter in order to decrease environmental and maximize any relevant genetic effect. Furthermore, participants with lifestyle factors known to affect vitamin D homeostasis were also excluded. We selected 23 target SNPs in five genes that encode key proteins of vitamin D metabolism (NADSYN1, GC, CYP24A1, CYP2R1, VDR).ResultsVariants in 2 genetic polymorphisms; rs2853564 (VDR) and rs11023374 (CYP2R1) showed a significant association with participants' BMI. These associations survived further adjustment for total-, free-, or bioactive-25(OH) vitamin D levels, although the variance explained by these 2 SNPS in BMI heterogeneity was only 3.2%.ConclusionOur results show two novel examples of the relationship between genetics of vitamin D and BMI, highlighting the potential role of vitamin D hormone in the physiology of obesity.
| S-EPMC7293123 | biostudies-literature
Project description:Significant reductions in prostate cancer incidence and mortality were observed in men randomized to receive 50 mg supplemental vitamin E (alpha-tocopherol) per day in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We hypothesized that variation in key vitamin E transport genes might directly affect prostate cancer risk or modify the effects of vitamin E supplementation. Associations between prostate cancer risk and 13 polymorphisms in two genes, TTPA and SEC14L2, were examined in 982 incident prostate cancer cases and 851 controls drawn from the ATBC Study. There was no association between the genetic variants and prostate cancer risk. Significant interactions were observed, however, between two variants in SEC14L2 (IVS11+931A>G and IVS11-896A>T) and the trial alpha-tocopherol supplement such that vitamin E supplementation reduced prostate cancer risk among men who were homozygous for either common allele [odds ratios (OR) and 95% confidence intervals (95% CI), 0.52 (0.30-0.90) and 0.64 (0.46-0.88), respectively] and nonsignificantly increased risk among those who carried one or two copies of either variant allele [ORs and 95% CIs, 1.27 (0.90-1.79) and 1.21 (0.96-1.52), respectively; both P for interaction < 0.05]. Genotype-phenotype analyses revealed significant but modest differences in baseline circulating concentrations of alpha-tocopherol and serum responses to the vitamin E supplementation for several polymorphisms. This study shows that genetic variation in TTPA and SEC14L2 is associated with serum alpha-tocopherol but does not have a direct effect on prostate cancer. Our results do, however, suggest that polymorphisms in SEC14L2 may modify the effect of vitamin supplementation regimens on prostate cancer risk.
| S-EPMC2644342 | biostudies-literature
Project description:BACKGROUND:The association between the Vitamin D Receptor (VDR) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several researches. However, the findings were inconsistent and inconclusive. Therefore, we set out a meta-analysis of all eligible published case-control studies to obtain an exact evaluation of the association between VDR gene polymorphisms and MS. METHOD:All relevant studies reporting the association between the VDR gene FokI (rs2228570), or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms and susceptibility to MS published up to May, 2019 were identified by comprehensive systematic search in the electronic database of web of science, Scopus, and PubMed. After that, the strength of association between VDR gene polymorphisms and susceptibility to MS was evaluated by odds ratio (OR) and 95% confidence interval (CI). RESULTS:A total of 30 case-control studies were included in the meta-analysis. The overall results suggested a significant association between TaqI polymorphism and MS risk under heterozygote genetic model (OR?=?1.27, 95%CI?=?1.01-1.59, random effect). Moreover, the pooled results of subgroup analysis declined presence of significant association under all defined genetic model. In subgroup analysis, BsmI polymorphisms was associated with increased risk of MS under recessive model in Asian populations. On the other hand, ApaI polymorphism was associated with decreased risk of MS under recessive and aa vs. AA model in Asian populations. CONCLUSION:This meta-analysis suggested a significant association between TaqI polymorphism and MS susceptibility. Furthermore, BsmI polymorphism was associated with increased risk of MS in Asian populations. In contrast, ApaI polymorphism was associated with decreased risk of MS in Asian populations. Future large-scale studies on gene-environment and gene-gene interactions are required to estimate risk factors and assist early diagnosis of patients at high risk for MS.
| S-EPMC6933912 | biostudies-literature
Project description:A super-enhancer (SE) is a cluster of enhancers with a relatively high density of particular chromatin features. SEs typically regulate key genes that can determine cell identity and differentiation. Identifying SEs and their effects may be critical in predicting key regulatory genes, such as master transcription factor genes or oncogenes. Signal inducible SEs are dense stretches of signal terminal transcription factor (TF) binding regions, and may modulate the interaction between environmental factors (e.g., Vitamin D) and genetic factors (i.e., risk variants) in complex diseases such as multiple sclerosis (MS). As a complex autoimmune disease, the etiology and progression of MS, including the interaction between Vitamin D and MS risk variants, is still unclear and can be explored from the aspect of signal SEs. Vitamin D [with its active form: 1,25(OH)2D3], is an environmental risk factor for MS. It binds the Vitamin D receptor (VDR) and regulates gene expression. This study explores the association between VDR super-enhancers (VSEs) and MS risk variants. Firstly, we reanalyse public ChIP-seq and RNA-seq data to classify VSEs into three categories according to their combinations of persistent and secondary VDR binding. Secondly, we indicate the genes with VSE regions that are near MS risk variants. Furthermore, we find that MS risk variants are enriched in VSE regions, and we indicate some genes with a VSE overlapping MS risk variant for further exploration. We also find two clusters of genes from the set of genes showing correlation of expression patterns with the MS risk gene ZMIZ1 that appear to be regulated by VSEs in THP-1 cells. It is the first time that VSEs have been analyzed, and we directly connect the genetic risk factors for MS risk with Vitamin D based on VSEs.
| S-EPMC6433938 | biostudies-literature
Project description:The vitamin D metabolite 1,25(OH)2D is the bioactive ligand of the vitamin D receptor (VDR). VDR forms a heterodimer with the retinoid X receptors (RXRs) that when bound to ligand influences the transcriptional control of genes that regulate circulating levels of vitamin D metabolites. Whether genetic variation in VDR or RXRA affects circulating levels of 1,25(OH)2D or 25(OH)D has not been established. We used a single nucleotide polymorphism (SNP) tagging approach to evaluate the association between SNPs in VDR and RXRA and serum levels of 1,25(OH)2D and 25(OH)D. A total of 42 tagSNPs in VDR and 32 in RXRA were analyzed in a sample of 415 participants. Principal components analyses revealed a gene-level association between RXRA and serum 1,25(OH)2D concentrations (P=0.01), but not 25(OH)D. No gene-level association was found for VDR with either serum biomarker. At the single-SNP level, a significant positive trend was observed for increasing 1,25(OH)2D levels with each additional copy of the A allele for RXRA SNP rs9409929 (P-trend=0.003). After a multiple comparisons adjustment, no individual SNP in VDR or RXRA was significantly associated with either outcome. These results demonstrate an association between genetic variation in RXRA and 1,25(OH)2D serum concentrations.
| S-EPMC2906637 | biostudies-literature
Project description:Vitamin D (VitD) is critical for the regulation of inflammatory processes, and VitD deficiency has been linked to several chronic inflammatory disorders. We aimed to investigate the concentrations of serum 25(OH)D3, lipid parameters, and three known VDR polymorphisms (BsmI, FokI, and TaqI) in patients with Familial Mediterranean fever (FMF), an autosomal recessive autoinflammatory disease. The study included 123 FMF patients and 105 controls. Seventy patients had no attack (group 1), 30 had 1-2 attacks (group 2), and 23 had 3 or more attacks (group 3) within last three months. Serum 25(OH)D3 concentrations were determined using liquid chromatography-tandem mass spectrometry. BsmI, FokI, and TaqI polymorphisms were analyzed by a competitive allele specific polymerase chain reaction assay (KASPar). Serum lipid parameters were measured with enzymatic colorimetric methods. 25(OH)D3 concentrations were lower in FMF patients compared to controls (p < 0.001). No difference was observed in 25(OH)D3 concentration between groups 1, 2, and 3. The distributions of FokI and TaqI genotypes were not significantly different between FMF patients and controls. There was a significant difference in the distribution of AA BsmI genotype between male FMF patients and male controls. Increased concentrations of triglycerides (p = 0.012) and decreased concentrations of high-density lipoprotein cholesterol [HDL-C] (p = 0.006) were found in FMF patients compared to controls. Although lower 25(OH)D3 concentrations were observed in FMF patients versus controls, no association was determined between FMF attack frequency and 25(OH)D3 concentrations. We showed that the AA genotype of BsmI polymorphism is associated with FMF in males but not in females. The effects of decreased HDL-C and increased triglyceride concentrations on cardiovascular events in FMF patients should be further investigated.
| S-EPMC5826670 | biostudies-literature
Project description:BackgroundLow vitamin B12 concentrations have been associated with major clinical outcomes, including adiposity, in Indian populations. The Fat mass and obesity-associated gene (FTO) is an established obesity-susceptibility locus; however, it remains unknown whether it influences vitamin B12 status. Hence, we investigated the association of two previously studied FTO polymorphisms with vitamin B12 concentrations and metabolic disease-related outcomes and examined whether these associations were modified by dietary factors and physical activity.MethodsA total of 176 individuals with type 2 diabetes, 152 with pre-diabetes, and 220 normal glucose-tolerant individuals were randomly selected from the Chennai Urban Rural Epidemiology Study. Anthropometric, clinical, and biochemical investigations, which included body mass index (BMI), waist circumference, vitamin B12, homocysteine, and folic acid were measured. A validated food frequency questionnaire was used for dietary assessment and self-reported physical activity measures were collected. An unweighted genetic risk score (GRS) was calculated for two FTO single-nucleotide polymorphisms (rs8050136 and rs2388405) by summation of the number of risk alleles for obesity. Interaction analyses were performed by including the interaction terms in the regression model.ResultsThe GRS was significantly associated with increased BMI (P = 0.009) and risk of obesity (P = 0.023). Individuals carrying more than one risk allele for the GRS had 13.13% lower vitamin B12 concentrations, compared to individuals carrying zero risk alleles (P = 0.018). No associations between the GRS and folic acid and homocysteine concentrations were observed. Furthermore, no statistically significant GRS-diet or GRS-physical activity interactions with vitamin B12, folic acid, homocysteine or metabolic-disease outcomes were observed.ConclusionThe study shows for the first time that a genetic risk score using two FTO SNPs is associated with lower vitamin B12 concentrations; however, we did not identify any evidence for the influence of lifestyle factors on this association. Further replication studies in larger cohorts are warranted to investigate the association between the GRS and vitamin B12 concentrations.
| S-EPMC6728975 | biostudies-literature
Project description:Vitamin D appears to have an important role in the modulation of the central nervous system. Vitamin D exerts its biological effects through its interaction with the vitamin D receptor (VDR). Located on chromosome 12 (12q13.1), the VDR gene has many different polymorphisms. Some of them are known to affect the VDR function, such as FokI (rs2228570, T/C) single nucleotide polymorphism. We aimed to explore a potential relationship between FokI VDR polymorphism and impulsiveness in alcohol-dependent (AD) patients. The study population consisted of 148 patients diagnosed with alcohol dependence (DSM-IV criteria) and 212 healthy controls. DNA was extracted from whole blood samples using the standard procedure. Genotypes were analyzed using a real-time PCR method. We found that FokI VDR gene polymorphism was associated with impulsivity [Barratt Impulsiveness Scale (BIS)-11 total score; P = 0.014], and with attentional impulsivity (BIS-11 subscale; P = 0.002) in the male AD patients. Our results suggest that CC FokI genotype of the VDR gene is associated with a higher level of impulsivity in these patients. This finding supports the hypothesis that impulsiveness, which significantly contributes to development of alcohol dependence, has a genetic background.
| S-EPMC4203996 | biostudies-literature
Project description: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.
| S-EPMC6412905 | biostudies-literature