Vitamin D Receptor Polymorphisms and Rheumatoid Arthritis Risk: A Systematic Review and Meta-Analysis Evaluating the Moderating Effects of Ethnicity, Bone Erosion, and Classification Criteria

Vitamin D receptor polymorphisms in primary biliary cirrhosis: A functional connection?

Vitamin D receptor (VDR) polymorphisms may play an important role in the vitiligo susceptibility. There have been many studies looking at the associations between VDR polymorphisms and vitiligo risk, but the conclusions are still up for debate. This study aimed to determine whether polymorphisms in the VDR are associated to the susceptibility to vitiligo. Vitamin D receptor polymorphisms in vitiligo patients and controls were identified using PubMed/Medline and Embase databases. The relationships between the VDR ApaI, TaqI, BsmI, and TaqI polymorphisms and vitiligo were investigated using meta-analyses of all participants and Asian, Arab, European, and Latin American groups. This meta-analysis included 13 papers with 2034 patients and 2771 controls. In all individuals, there was no link between vitiligo and the VDR ApaI A allele (OR=0.889, 95% CI=0.713-1.109, p=0.298). However, in Asians (OR=0.721, 95% CI=0.553-0.940, p=0.016) but not in Europeans or Arabs, there was a link between the VDR ApaI A allele and vitiligo. Utilizing recessive, dominant, and homozygote contrast models, a link between vitiligo and the VDR ApaI polymorphism was discovered in Asians. Meta-analysis of the VDR BsmI polymorphism showed a significant association between vitiligo and the B allele (OR=0.812, 95% CI=0.686-0.961, p=0.015). In contrast, no connection between vitiligo and VDR polymorphisms was identified for TaqI and FokI polymorphisms. In the Asian population, ApaI and BsmI polymorphisms in VDR have been correlated to vitiligo susceptibility. However, TaqI and FokI polymorphisms in VDR are not associated with vitiligo susceptibility in European, Asian, Arab, and Latin American populations.

The aim of this study was to determine whether the vitamin D receptor (VDR) polymorphisms confer susceptibility to rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). A meta-analysis was conducted on the associations between the BsmI, TaqI, FokI, and ApaI polymorphisms of VDR and RA or SLE using: (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) additive model. A total of ten studies, six RA and four SLE studies, were considered in the meta-analysis. Meta-analysis of the VDR BsmI and TaqI polymorphisms showed no association between RA in all subjects, or in European or Asian subjects. In contrast, meta-analysis of the F allele, the FF genotype, and the FF vs. the ff genotype of the FokI polymorphism showed significant associations with RA in Europeans. The overall OR of the association between the F allele and RA was 1.502 (95% CI=1.158-1.949, P=0.002). Meta-analysis of the B allele, BB+Bb genotype, and BB genotype (additive model) of the BsmI polymorphism showed significant associations with SLE and LN in Asians. The overall ORs of the associations between the B allele and SLE and LN were 3.584 (95% CI=1.407-9.130, P=0.007) and 3.652 (95% CI=1.347-9.902, P=0.011). This meta-analysis demonstrates that the VDR FokI polymorphism may confer susceptibility to RA in Europeans. Furthermore, associations were found between the VDR BsmI polymorphism and susceptibilities to SLE and LN in Asians.

Background Objectives To determine whether 1) the frequency of vitamin D receptor (VDR) polymorphisms in the rheumatoid arthritis (RA) patient group is different from that of the control group; and 2) there is a relationship between VDR genotypes vs the radiographic severity of RA and bone mineral density (BMD) in RA patients in Korea. Methods The VDR genotype was determined by using polymerase chain reaction and by digestion with three restriction enzymes Taq I and Bsm I in elderly female controls (n = 78) and RA patients (n = 97). Hand X-rays were scored by Larsen’s method and femoral neck BMD was measured by dual energy X-ray absorptiometry in RA patients. Results VDR genotypic distributions in Koreans were much different from those of Caucasians in both the control and RA group. In particular, “tt” and “BB” alleles were very rare, unlike the distribution in Caucasian population. No significant differences in VDR genotypic frequency were observed between the control group and the RA group. In addition, no significant relationship was found between the VDR genotypes and radiographic scores of RA, nor between the VDR genotypes and BMD in RA patients. Conclusion The distribution of VDR polymorphisms in RA patients is not different from that of the controls. The VDR polymorphisms do not significantly correlate with the radiographic severity of RA, nor with BMD in Korean RA patients.

Vitamin D receptor TaqI, BsmI and ApaI polymorphisms and osteoarthritis susceptibility: A meta-analysis

We performed this study to investigate the possible association between vitamin D receptor (VDR) gene polymorphism and the focal bone erosion in rheumatoid arthritis (RA) patients in Korea. One hundred and fifty-seven RA patients were enrolled and two control groups were selected. The focal bone erosion score was assessed by modified Sharp's method. Genotyping of VDR polymorphisms was performed by polymerase chain reaction and restriction fragment length polymorphism analysis using two restriction enzyme Taq I and Bsm I. Notably, the distribution of VDR genotype in Korean population was different from Caucasians. The frequencies of "tt" and "BB" genotypes were very rare both in RA patients and in control groups. The frequency distribution of the Taq I and Bsm I genotype was not different between RA patients (TT, 93.6%; Tt, 6.4%; tt, 0%; BB, 0.6%; Bb, 5.1%; bb, 94.3%) and control groups (TT, 90.8%; Tt, 7.5%; tt, 1.7%; BB, 1.4%; Bb, 8.1%; bb, 90.5%). There was no significant difference in the focal bone erosion score (mean +/- SD) according to the VDR genotypes of RA patients (TT, 0.92 +/- 1.79; Tt, 0.4 +/- 0.79; Bb, 0.43 +/- 0.80; bb, 0.92 +/- 1.79; p > 0.05). In conclusion, these results suggest that VDR gene polymorphisms are not associated with the focal bone erosion in RA patients in Korea.

Objective Many studies demonstrate associations between UVB rays and a lower risk of developing various cancers, implying that UVB rays induce vitamin D synthesis, which suppresses growth and induces differentiation/apoptosis of cancer. In patients with non-small-cell lung cancer, vitamin D receptor (VDR) polymorphisms and haplotypes are reported to be associated with survival. We hypothesized that a similar association would be observed in other type of cancers. In this study, we focused on head and neck squamous-cell carcinoma (HNSCC). Methods DNA was extracted from the frozen tumor and the VDR polymorphisms (Cdx2, FokI and BsmI) in 97 patients with HNSCC were genotyped by sequencing. Disease-free survival was compared between VDR polymorphisms using Kaplan-Meier survival with log-rank tests and using the Cox proportional hazard model adjusted for age, gender, primary tumor site, and postoperative stages. Adjusted hazard ratios (AHR) and 95% confidence intervals (95% CI) were determined. Results Tumor recurrence occurred in 41/97 (42%) patients during a median follow-up of 603 days. Genotype frequencies of the VDR polymorphisms were as follows: FokI: C/C, 39 (40%); C/T, 48 (50%); TT, 10 (10%); for Cdx2: G/G, 16 (17%); G/A, 41 (42%); A/A, 40 (41%) Bsm I: A/A, 5 (5.2%); A/G, 16 (16.5%); and G/G, 76 (78.3%). The FokI T/T genotype was associated with poor prognosis: median survival for T/T was 265 days compared with 959 days for C/C or C/T (log-rank: P=0.015; AHR, 2.65; 95% CI, 1.18 to 5.96; P=0.018). In contrast, Cdx2 and BsmI showed no significant association with survival. The G-T (Cdx2-FokI) haplotype was associated with worse disease-free survival compared with other haplotypes: median disease-free survival for G-T was 238 days compared with 959 days for other haplotypes (log-rank: P=0.0008; AHR, 6.67; 95% CI, 2.23 to 20.0; P=0.001). Conclusion These results suggest that VDR polymorphisms and haplotypes may be associated with prognosis of patients with HNSCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 23. doi:10.1158/1538-7445.AM2011-23

Vitamin D and its receptor polymorphisms are associated with glaucoma

THU0010 Vitamin d and oestrogen receptor polymorphism in rheumatoid arthritis

Contribution of VDR polymorphisms to type 1 diabetes susceptibility: Systematic review of case–control studies and meta-analysis

Association between vitamin D receptor polymorphism and type 2 diabetes or metabolic syndrome in community-dwelling older adults: The Rancho Bernardo Study

BackgroundStudies on the susceptibility of vitamin D receptor (VDR) polymorphisms to coronary artery disease (CAD) reached controversial results. We performed this study for a more accurate evaluation between the VDR polymorphisms and CAD susceptibility.MethodsPubMed, Embase, CNKI, Wan Fang, and VIP databases were searched. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to evaluate the associations. Trial sequential analysis (TSA) was introduced to estimate the positive associations. The potential functions of the VDR polymorphisms were analyzed based on the SNPinfo and ENSEMBL databases.ResultsThirteen studies were finally included. In the overall analysis, increased CAD risks were observed in the VDR rs1544410 polymorphism and verified by the TSA; for the rs2228570 and rs731236 polymorphisms, significant associations with high heterogeneity were detected; decreased risk was remarkably observed for the rs7975232 polymorphism. In the subgroup analysis, wide associations with reduced heterogeneity were observed in the rs2228570, rs1544410, and rs731236 polymorphisms. The RNAfold analysis indicated the mutant G allele of the rs1544410 polymorphism was easier to disperse from the DNA double helix structure and may have a potential crucial role in the VDR transcription process.ConclusionsOur analysis supports the role of the rs1544410 polymorphism in the VDR gene as a risk factor for CAD. The VDR rs2228570 and rs731236 polymorphisms were associated with increased CAD risks in the White population. Restrict decreased CAD risk was firstly discovered in the rs7975232 polymorphism.LimitationsFirstly, the language was restricted to English and Chinese, which will cause the limited number of studies included; secondly, other unknown polymorphisms in VDR polymorphisms could also be associated the CAD susceptibility, and more case-control studies with comprehensive clinical outcomes and GWAS studies were required; thirdly, the rs1544410, rs7975232 and rs731236 polymorphism are in strong LD, haploid factors with CAD risk need to be considered; fourthly, the mechanisms of the VDR polymorphism on the VDR gene or RNA or protein were not discussed enough, further mechanistic studies are required; at last, genetic factor was the one side for CAD susceptibility, the interaction between environmental risk factors should be considered.

Association between vitamin D receptor polymorphism and breast cancer in women: An umbrella review of meta-analyses of observational investigations

Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in multiple sclerosis (MS). However, published studies demonstrated differences concerning design and effect size. A meta-analysis is necessary to determine the magnitude of the association between VDR polymorphisms and MS risk. The aim of the current study was to quantify the magnitude of the association between BsmI, FokI, ApaI, and TaqI VDR polymorphisms and MS risk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search and meta-analysis of the VDR gene polymorphisms and the risk of MS. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated by using Stata Version 11.0 with dominant and recessive models and allele analyses. A total of 4013 cases and 4218 controls in 24 case-control studies were included in the meta-analyses. The results did not indicate an association between any of the VDR polymorphisms and the risk of MS among overall populations, Asians, and Caucasians. However, our subgroup analysis suggests that the A allele was associated with MS risk in Asian populations (P=0.005, OR=1.267, 95% CI 1.074-1.496). Interestingly, the sensitivity analysis excluding studies with controls not in HWE showed insignificant association between the A allele and MS risk (P=0.211), which was different from those in the non-sensitivity analysis. Our preliminary results indicate the VDR gene ApaI, BsmI, FokI, and TaqI polymorphisms may not be associated with elevated MS risk among overall populations. But ApaI polymorphism may confer different susceptibility to MS among different populations, and more well-designed studies with a large sample size are still needed to validate our results.

Vitamin D participates in the calcification of enamel and dentin and the appropriate immune responses to oral microbial infections. We aimed to assess the association between the most common vitamin D receptor (VDR) polymorphisms (ApaI, FokI, TaqI, BsmI, and BglI) and the risk of dental caries in children. Methods: PubMed/MEDLINE, Cochrane Library, Web of Science, and Scopus databases were comprehensively searched until 19 January 2021. Meta-analysis with odds ratios as the effect estimate along with 95% confidence intervals and subgroup analysis were conducted using Review Manager 5.3 software. Publication bias and sensitivity analyses were conducted by Comprehensive Meta-Analysis, version 2.0 software. Results: Seventy-eight studies were retrieved from the databases, with nine studies included in the final analysis. Based on five genetic models, there was no association between ApaI (rs7975232), TaqI (rs731236), BsmI (rs1544410), FokI (rs2228570), and BglI (rs739837) polymorphisms and susceptibility to dental caries, except for the FokI (rs10735810) polymorphism. Conclusion: Among the VDR polymorphisms considered, an association was found between the FokI (rs10735810) polymorphism and the risk of dental caries, with a protective role of the f allele and ff genotype.