Rs2228570 Variants Research Articles

Association of vitamin D levels and VDR variant (rs2228570) with allergic rhinitis: A meta-analysis and trial sequential analysis

BackgroundAllergic rhinitis (AR) is a most common allergic condition characterised by cough, sneezing and flu-like symptoms. The aetiology of AR is not known. A deficiency of vitamin D has been associated with various allergic diseases. The role of vitamin D in allergic rhinitis has been explored in different populations, but the results remained inconsistent. Furthermore, vitamin D exerts its effect through the vitamin D receptor (VDR), and genetic variations in the VDR gene significantly alter vitamin D. We performed a meta-analysis to investigate the role of vitamin D levels and VDR polymorphisms with a predisposition to the development of AR. Materials and methodsAll published articles were searched using databases such as PubMed, Google Scholar, and Science Direct. Based on rigorous inclusion and exclusion, appropriate studies were identified. Vitamin D levels, VDR genotype and allele frequencies were extracted from the eligible reports. The meta-analysis was performed by comprehensive meta-analysis software v3.3. ResultsThe present meta-analysis comprised 14 reports with 1504 AR patients and 1435 healthy controls. Compared to healthy controls, AR had significantly lower levels of vitamin D (P = 0.000, standard difference of means = −1.287, 95% CI = −1.921 to −0.652). The meta-analysis of two separate investigations, which included 917 cases and 847 controls, showed no predisposition to allergic rhinitis. The trial sequential analysis also demonstrated the need for future case-control studies of VDR polymorphism to examine their involvement in AR. ConclusionsLower vitamin D levels are associated with allergic rhinitis, and vitamin D supplementation might be advantageous in addition to standard treatment. The connection of VDR polymorphism (rs2228570) remained equivocal, and additional research is needed. SummaryVitamin D exerct its beneficial effect through the vitamin D receptor (VDR) and role of vitamin D and VDR variant in the allergic rhinitis has been contradictories. We performed a meta-analysis to draw a definitive conclusion of importance of vitamin D and VDR polymorphisms in predisposition to development of allergic rhinitis. The observations of the meta-analysis revealed a significant association of lower vitamin D with allergic rhinitis. In addition the VDR rs2228570 variant predisposed subject to develop rhinitis. Collectively, the results of the present investigation redirect requirement of individualized vitamin D supplementation in the management of allergic rhinitis.

D Vitamini Serum Düzeyleri ile D Vitamini Metabolizmasındaki Kritik Genlere Ait Varyasyonların Beyin Kanserinde İncelenmesi

Recent studies imply the effects of micronutrient intake on the development of several cancers including primary brain cancer (PBC). The biological effects of vitamin D, a member of the fat-soluble vitamin family acting as a steroid hormone, was carried out by binding its receptor (VDR) through vitamin D-binding-protein (VDBP). The present study aims to investigate the effects of vitamin D levels and VDR rs2228570, VDR rs731236, VDBP 7041 polymorphisms on PBC development. The study group consisted of 71 patients and 84 controls. Vitamin D levels were determined by high-pressure liquid chromatography where polymorphisms by polymerase-chain-reaction and restriction fragment length polymorphism methods. The distribution of VDR rs2228570 variants in PBC and its subgroups were determined as FF>Ff>ff; VDBP rs7041 variants were TG> GG>TT, however, VDR rs731236 variants were Tt>TT>tt in PBC and meningioma and TT>Tt>tt in glioma. Vitamin D levels were measured below normal levels in all patients and control groups, which shows the deficiency in Turkish society in line with the literature. Our results show that low serum vitamin D level may be an individual risk factor in the development of brain tumors, however, VDR rs2228570 and rs731236 and VDBP rs7041 polymorphisms have no effect on the risk of disease development. 

Associations between vitamin D receptor genetic variants and tuberculosis: a meta-analysis.

We performed a meta-analysis to evaluate potential associations between vitamin D receptor (VDR) genetic variants and tuberculosis (TB). Systematic literature research was conducted in PubMed, Web of Science, and Embase. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to estimate strength of associations in all possible genetic models, and P values ≤ 0.05 were considered to be statistically significant. In total, 42 studies were enrolled for analyses. Pooled overall analyses suggested that VDR rs1544410 (dominant model: P = 0.02; allele model: P = 0.03) and rs731236 (dominant model: P = 0.04; recessive model: P = 0.02; allele model: P = 0.01) variants were significantly associated with TB. Further subgroup analyses by ethnicity revealed that rs1544410 (dominant and allele models) and rs731236 (dominant, recessive, and allele models) variants were both significantly associated with TB in South Asians. When we stratified data by type of disease, positive results were detected for rs7975232 variant in EPTB (dominant, recessive, over-dominant, and allele models) subgroup, and for rs2228570 variant in PTB (dominant, recessive, and allele models) and EPTB (dominant, recessive, over-dominant, and allele models) subgroups. Our meta-analysis supported that rs7975232, rs1544410, rs2228570, and rs731236 variants might serve as genetic biomarkers of certain types of TB.

Associations between vitamin D receptor genetic variants and periodontitis: a meta-analysis

Objective: Numerous studies already investigated potential associations between vitamin D receptor (VDR) genetic variants and periodontitis. However, the results of these studies were not consistent. Previous studies failed to reach a consensus regarding associations between VDR variants and periodontitis partially because of their relatively small sample sizes. Thus, we performed the present meta-analysis to explore the relationship between VDR variants and periodontitis in a larger pooled sample size.Material and methods: Systematic literature research was conducted in PubMed, Web of Science, Embase and CNKI to identify eligible case-control studies on associations between VDR variants and periodontitis. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the strength of associations in all possible genetic models, and p values ≤.05 were considered to be statistically significant.Results: Totally 30 studies were enrolled for analyses. Pooled analyses suggested that VDR rs2228570 variant was significantly associated with the susceptibility to periodontitis under dominant genetic model in the overall population (p = .03, OR = 0.82, 95%CI: 0.69–0.98, I2 = 0). Further subgroup analyses yielded similar positive results for rs2228570 variant in East Asians and patients with chronic periodontitis. Nevertheless, no any other positive findings were observed in overall and subgroup analyses.Conclusions: Our meta-analysis supported that VDR rs2228570 variant might serve as a genetic biomarker of periodontitis. However, further well-designed studies are still warranted to confirm our findings.

A systematic review and meta-analysis of the associations of vitamin D receptor genetic variants with two types of most common neurodegenerative disorders.

Whether vitamin D receptor (VDR) genetic variants influence individual susceptibility to neurodegenerative disorders remains controversial. This meta-analysis was conducted to analyze correlations of VDR genetic variants with two types of most common neurodegenerative disorders, Parkinson's disease (PD) and Alzheimer's disease (AD). Systematic literature research of PubMed and Embase was performed to identify eligible articles. Q test and I2 statistic were employed to decide whether pooled analyses would be performed with random-effect models (REMs) or fixed-effect models (FEMs). All statistical analyses were conducted with Review Manager. Totally sixteen studies were enrolled for analyses. Among these eligible studies, ten studies were about PD (2356 cases and 2815 controls) and six studies were about AD (1256 cases and 1205 controls). Pooled overall analyses suggested that VDR rs7975232 (additive model: p = 0.03, OR = 1.19, 95% CI 1.01-1.39) and rs2228570 (recessive model: p < 0.008, OR = 1.26, 95% CI 1.06-1.50; allele model: p < 0.001, OR = 0.80, 95% CI 0.71-0.91) variants were significantly correlated with PD, and VDR rs731236 (dominant model: p = 0.003, OR = 0.70, 95% CI 0.56-0.89; additive model: p = 0.02, OR = 1.32, 95% CI 1.06-1.66; allele model: p = 0.02, OR = 0.82, 95% CI 0.69-0.96) variant was significantly correlated with AD. Further subgroup analyses by ethnicity revealed that the positive results were mainly driven by the Asians, whereas no significant associations were observed in Caucasians. Our meta-analysis suggested that VDR rs7975232 and rs2228570 variants might serve as genetic biomarkers of PD, whereas VDR rs731236 variant might serve as a genetic biomarker of AD.

A meta-analysis on associations between vitamin D receptor genetic variants and tuberculosis

ObjectivesWe aimed to analyze potential associations between vitamin D receptor (VDR) genetic variants and tuberculosis (TB) through a meta-analysis. MethodsSystematic literature research of PubMed, Web of Science, Embase and CNKI was performed to identify eligible articles. Statistical analyses were conducted by using Review Manager. ResultsTotally 54 studies were enrolled for analyses. Pooled overall analyses suggested that VDR rs1544410 (dominant model: p = 0.02; allele model: p = 0.04), rs2228570 (recessive model: p = 0.01; allele model: p = 0.03) and rs731236 (recessive model: p = 0.02; allele model: p = 0.02) variants were significantly associated with TB. Further subgroup analyses by ethnicity revealed that rs1544410 variant was significantly associated with TB in South Asians (dominant and allele models) and Caucasians (dominant, recessive and allele models), rs2228570 variant was significantly associated with TB in East Asians (recessive model), and rs731236 variant was significantly associated with TB in South Asians (dominant, recessive and allele models). ConclusionsOur meta-analysis suggested that VDR rs1544410, rs2228570 and rs731236 variants might serve as genetic biomarkers of TB in certain populations.

Vitamin D receptor polymorphism rs2228570 is significantly associated with risk of dyslipidemia and serum LDL levels in Chinese Han population

BackgroundThe goal of this study was to determine if vitamin D receptor (VDR) gene polymorphisms underlie susceptibility to dyslipidemia in a Chinese Han population.MethodsThree tag single nucleotide polymorphisms (SNPs) (rs11574129, rs2228570, and rs739837) were genotyped using TaqMan assays to determine VDR SNP associations with dyslipidemia. We genotyped 877 cases of dyslipidemia from a normotensive, non-diabetes mellitus population and 1822 non-dyslipidemia subjects in a stage I study. In a follow-up stage II study, we included a larger sample of 3124 controls and 1679 cases with dyslipidemia. Finally, we explored the potential molecular mechanism for the SNP associations using molecular modeling analysis.ResultsWe found a significant association between SNP rs2228570 and dyslipidemia in the additive (adjusted odds ratio (OR) = 1.255, 95% Confidence Interval (CI) = (1.118–1.409), P < 0.001), dominant (OR = 1.384, 95% CI = 1.384 (1.136–1.6), P = 0.001) and recessive models (OR = 1.356, 95%CI = 1.1–1.671, P = 0.004) in stage I. We further established that the rs2228570 variant was significantly associated with dyslipidemia in the additive (adjusted OR = 1.146, 95% CI = 1.053–1247, P = 0.002), dominant (OR = 1.184, 95%CI =1.018–1.376, P = 0.028) and recessive models (OR = 1.209, 95%CI = 1.064–1.374, P = 0.004) in stage II. The TT genotype was significantly higher (4.93 ± 0.75 mmol/L) compared to the TC (4.67 ± 0.47 mmol/L) or CC (4.66 ± 0.44 mmol/L) genotype (P = 0.01) in cases with elevated low-density lipoprotein cholesterol (LDL-C) levels. In contrast, the cases with the TT genotype had significantly lower serum 25(OH)D levels (18.43 ± 5.04 ng/ mL) compared to the TC (26.24 ± 4.16 ng/mL) and CC (36.76 ± 8.10 ng/ mL) genotypes (P < 0.001). Multivariable linear regression analysis indicated that the rs2228750 genotype significantly correlated with serum low-density lipoprotein-C (LDL-C) levels in cases with dyslipidemia. Using molecular modeling analysis, we further found that the rs2228570 variant changed the structure and the stability of VDR and altered the binding energy of its ligand.ConclusionsThe VDR rs2228570 variant may increase susceptibility to dyslipidemia in the Chinese Han population.