Vitamin D receptor gene BsmI, FokI, ApaI and TaqI polymorphisms and the risk of systemic lupus erythematosus

Recently, several studies have demonstrated the role of vitamin D receptor (VDR) polymorphisms in the development of systemic lupus erythematosus (SLE); however, these results are inconsistent between different cohorts. Therefore, we studied the prevalence of the VDR FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) genotypes and alleles in SLE patients (n = 258) and healthy individuals (n = 545) in a Polish population. We did not observe significant differences for either the VDR FokI, BsmI, ApaI and TaqI genotype and allele frequencies in patients with SLE and healthy individuals. However, the frequency of the VDR F/F and F/f genotypes of FokI was statistically different between patients with renal disease and patients without this symptom OR = 3.228 (1.534–6.792, p = 0.0014), p _corr = 0.0476)]. There was no association of the studied VDR BsmI, ApaI and TaqI polymorphisms with clinical manifestations and laboratory profiles in patients with SLE. Our study indicates that the studied VDR FokI variant might increase the risk of some clinical presentations in patients with SLE.     

A multiplex single-base extension protocol for genotyping Cdx2, FokI, BsmI, ApaI, and TaqI polymorphisms of the vitamin D receptor gene

The well-described role of the vitamin D endocrine system in bone metabolism makes its receptor a widely investigated candidate gene in association studies looking for the genetic basis of complex bone-related phenotypes. Most association studies genotype five polymorphic sites along the gene using PCR-RFLP and allele-specific amplification methods, which may not be the better choice in large case/control or cross-sectional studies. In this case, genotyping SNPs in parallel and using automated allele-calling methods are important to decrease genotyping errors due to manual data handling and save sample in cases where the amount of DNA is limited. The aim of this study was to present a straightforward method based on multiplex PCR amplification followed by multiplex single-base extension as a simple way to genotype five vitamin D receptor gene polymorphisms in parallel, which may be implemented in medium- to large-scale case/control or cross-sectional studies. The results regarding method feasibility and optimization are presented by genotyping eight paternity trios and seven samples of Brazilian postmenopausal women who took part in an ongoing association study carried out by members of our group.     

Quantitative assessment of the associations between four polymorphisms (FokI, ApaI, BsmI, TaqI) of vitamin D receptor gene and risk of diabetes mellitus

The vitamin D receptor (VDR) gene polymorphisms have been suggested to be involved in the development of diabetes mellitus, including type 1 diabetes (T1DM) and type 2 diabetes (T2DM). However, the results have been inconsistent. In this study, we performed a meta-analysis to investigate the associations. Literature was retrieved from PubMed, ISI Web of Science and Chinese databases. Pooled odds ratios (ORs) with 95?% confidence intervals (CIs) were calculated using a random or fixed effect model. 79 studies (FokI: 22 studies; BsmI: 25 studies; ApaI: 17 studies; TaqI: 15 studies) on T1DM and 44 studies (FokI: 10 studies; BsmI: 10 studies; ApaI: 14 studies; TaqI: 10 studies) on T2DM were included. The results indicated that BsmI polymorphism was associated with an increased risk of T1DM (B vs. b: OR 1.31, 95?% CI 1.10-1.55, P?=?0.002), especially in East Asians (B vs. b: OR 2.57, 95?% CI: 1.55-4.24, P?相似文献   

The vitamin D receptor gene variants,ApaI, TaqI,BsmI, and FokI in diabetic foot ulcer and their association with oxidative stress

Molecular Biology Reports - To date, numerous disorders have been linked to vitamin D deficiency. Several lines of evidence indicate a relationship between vitamin D deficiency and the risk of...     

Evaluation of vitamin D receptor (VDR) gene polymorphisms (FokI, TaqI and ApaI) in a family with dentinogenesis imperfecta

Dentinogenesis imperfecta Type II (DGI-II) is a condition inherited as an autosomal dominant trait and characterized by abnormal dentine structure affecting both the primary and secondary dentitions. The genetic etiology of the disease still remains unclear, suggesting a genetically heterogeneous background. The aim of this study is to manifest briefly DGI-II and to investigate the association between BsmI, TaqI and FokI polymorphisms of vitamin D receptor (VDR) gene and dentinogenesis imperfecta type II in a Turkish family by PCR-RFLP methodology. The affected mother and her two affected daughters were bb for BsmI polymorphism, whereas her unaffected son and her husband were Bb for the same polymorphism. One of the affected children was tt, the rest of the family were Tt for TaqI polymorphism, and all of the enrolled subjects were FF for FokI polymorphism. As a conclusion, BsmI polymorphism bb seems to be associated with (DGI-II), but should be examined in larger numbers in order to be considered as a risk factor.     

Vitamin D receptor gene polymorphisms (TaqI and ApaI) in relation to 25-hydroxyvitamin D levels and coronary artery disease incidence

Abstract

Context/objective: Previous studies have illustrated the association of the ApaI and TaqI polymorphisms of the vitamin D receptor gene, located in non-coding and coding regions, respectively, with diseases such as cancer and cardiovascular disease; however, investigating such association in Egyptian patients with coronary artery disease (CAD) has never been formerly attempted. Materials and methods: Male patients (n?=?137), 35–50 years of age, with verified CAD, were recruited alongside age- and sex-matched controls (n?=?58). Genotyping and 25-hydroxyvitamin D [25(OH)D] measurement were performed by polymerase chain reaction RFLP and HPLC, respectively. Results: Comparison of the genotypic distribution of both the TaqI and ApaI polymorphisms between patients and controls yielded insignificant results (p?=?0.55 and 0.7, respectively). Comparison of the allelic distribution of both polymorphisms also yielded insignificant results. The TaqI polymorphism was not found to predict 25(OH)D levels, whereas the wild-type genotype of the ApaI polymorphism was associated with greater levels of 25(OH)D (p?=?0.02), taking all subjects into consideration. Discussion/conclusion: This study presents the ApaI and TaqI polymorphisms as non-influencing players in the pathogenesis of CAD in Egyptian males and the ability of only the ApaI polymorphism to predict 25(OH)D levels, thus warranting further investigations of the triangular relationship between the polymorphisms, 25(OH)D and CAD incidence.     

Association of vitamin D receptor FokI and ApaI polymorphisms with lung cancer risk in Tunisian population

Many studies reported that Vitamin D Receptor (VDR) gene polymorphisms might influence the cancer risk due to their antiproliferative, antiangiogenic, and apoptotic effects. The aim of this study was to explore the genetic association of VDR polymorphisms with lung cancer risk in Tunisian population. The genotype and haplotype frequencies of four VDR polymorphisms, FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were studied using polymerase chain reaction and restriction fragment length polymorphism analysis in 240 patients with lung cancer and 280 healthy controls. The distribution of genotype frequencies differed significantly between lung cancer subjects and controls (FokI P _adj  = 0.002; ApaI P _adj  = 0.013). Haplotype analyses revealed a significant association between G-A-C and A-C-T haplotypes and lung cancer risk (P _corr  = 0.0128, P _corr  = 0.008). When patients were stratified according to gender, age, and smoking, significant associations were detected with FokI and TaqI polymorphisms. We found a lack of association between BsmI, TaqI polymorphisms and lung cancer risk (P > 0.05). Only, the attributable proportion due to interaction and the synergic index for interaction between ApaI polymorphism and smoking were statistically significant (P _adj  = 0.74, 95 % CI = 0.38–1.20) and (P _adj  = 0.63, 95 % CI = 0.05–1.21), respectively. Both the additive interaction measures suggested the existence of a biological interaction between SNP ApaI, but not FokI, and smoking. The multiplicative interaction measure was not statistically significant (P > 0.05). This is the first study in Tunisia, which suggested that VDR FokI and ApaI polymorphisms might be risk factors for lung cancer development.     

Vitamin D receptor TaqI and ApaI polymorphisms: A comparative study in patients with Behçet’s disease and Rheumatoid arthritis in Tunisian population

Recent genetic surveys have identified vitamin D receptor (VDR) as a susceptibility gene for several autoimmune diseases. This study was designed to investigate the association of VDR gene polymorphisms with Behçet’s disease (BD) and Rheumatoid arthritis (RA). A case–control study including 151 BD, 106 RA patients and an appropriate number of healthy control subjects were performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Association between TaqI polymorphism and BD was marginal under codominant and recessive models (P = 0.078 and P = 0.058, respectively). After stratification, we found evidence for a significant association between TaqI polymorphism and BD in the elderly subjects (P = 0.037). The minor ApaI a allele tended to confer an increased risk for BD susceptibility (P = 0.087). BD patients with VDR homozygous AA or aa genotypes were at increased risk for development of erythema nodosum (EN) skin manifestation (P = 0.038). No significant association was observed for VDR ApaI and TaqI polymorphisms with RA risk (P > 0.05). TaqI and ApaI polymorphisms might be modestly implicated in BD pathogenesis. They could be considered as potential biomarkers in BD rather than susceptibility genes. However, TaqI and ApaI seemed not to be implicated in RA pathogenesis.     

Vitamin D receptor gene BsmI polymorphisms in Thai patients with systemic lupus erythematosus

The immunomodulatory role of 1,25-dihydroxyvitamin D3 is well known. An association between vitamin D receptor (VDR) gene BsmI polymorphisms and systemic lupus erythematosus (SLE) has been reported. To examine the characteristics of VDR gene BsmI polymorphisms in patients with SLE and the relationship of polymorphisms to the susceptibility and clinical manifestations of SLE, VDR genotypings of 101 Thai patients with SLE and 194 healthy controls were performed based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The relationship between VDR gene BsmI polymorphisms and clinical manifestations of SLE was evaluated. The distribution of VDR genotyping in patients with SLE was 1.9% for BB (non-excisable allele homozygote), 21.78% for Bb (heterozygote), and 76.23% for bb (excisable allele homozygote). The distribution of VDR genotyping in the control group was 1.03% for BB, 15.98% for Bb, and 82.99% for bb. There was no statistically significant difference between the two groups (p = 0.357). The allelic distribution of B and b was similar within the groups (p = 0.173). The relationship between VDR genotype and clinical manifestation or laboratory profiles of SLE also cannot be statistically demonstrated. In conclusion, we cannot verify any association between VDR gene BsmI polymorphism and SLE. A larger study examining other VDR gene polymorphisms is proposed.     

Start codon FokI and intron 8 BsmI variants in the vitamin D receptor gene and susceptibility to colorectal cancer

Epidemiological evidence suggests the protective effect of vitamin D against colorectal cancer (CRC) and the polymorphisms in vitamin D receptor (VDR) gene may influence the development of CRC. In this study the possible association of VDR FokI and BsmI gene polymorphisms with CRC risk was examined. A total of 904 subjects, including 452 cases with CRC and 452 controls were enrolled in this study. All 904 subjects were genotyped for VDR FokI and BsmI gene polymorphisms by PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between the cases with CRC and controls for the both FokI and BsmI polymorphisms either before or after adjustment for confounding factors including age, BMI, sex, and smoking status. Furthermore, no evidence for effect modification of the association VDR gene FokI and BsmI variants and CRC by BMI, sex, or tumor site was observed. In addition, there was no significant difference in genotype and allele frequencies between the normal weight (BMI <25 kg/m²) cases with CRC and overweight/obese (BMI ≥25 kg/m²) cases with CRC for the two SNPs. Our results do not lend support to the hypothesis that VDR gene FokI and BsmI polymorphisms are associated with the risk of CRC. However, further studies are required to confirm this finding.     

Association of Vitamin D Receptor Polymorphisms (FokI (Rs2228570), ApaI (Rs7975232), BsmI (Rs1544410), and TaqI (Rs731236)) with Gastric Cancer in a Kurdish Population from West of Iran

Background:The association of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) and its receptor, vitamin D receptor (VDR), with cancer types have been studied. However, there are controversial findings regarding the association of specific VDR polymorphisms with different kinds of cancers. In the current study, we investigated the association of VDR polymorphisms (Fok1 (rs2228570), ApaI (rs7975232), BsmI (rs1544410), and TaqI (rs731236)) with the risk of gastric cancer in a Kurdish population of Kermanshah in Iran for the first time. Methods:In this case-control study, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used in 99 gastric cancer patients and 100 healthy subjects as controls.Results:The frequencies of f (FokI), b (BsmI), t (TaqI), and a (ApaI) alleles were: 55.6%, 27.3%, 62.1%, and 44.95% in the patient group, respectively and 42%, 29.5%, 54.5%, and 46.0% in the control group, respectively. Analysis of the results indicated that there was a positive association between the frequency of FokI genotypes with gastric cancer risk (p= 0.021). However, no statistically significant association of BsmI, Taq1, and ApaI polymorphisms of VDR was detected in gastric patients when compared with healthy individuals.Conclusion:VDR-FokI polymorphism could increase the risk of GC development and predispose to the disease by mechanisms.Key Words: Gastric cancer, PCR-RFLP, Polymorphism, Vitamin D receptor     

Vitamin D receptor gene polymorphisms,bone mineral density and bone turnover: FokI genotype is related to postmenopausal bone mass

The relationship between vitamin D receptor (VDR) intragenic polymorphisms FokI, BsmI, ApaI and TaqI and bone mineral density (BMD) or biochemical markers of bone remodeling were investigated in 114 Czech postmenopausal women, on the average 62.5+/-8.9 years of age. Restriction fragment length polymorphisms in the VDR gene were assessed by PCR amplification and digestion with restriction enzymes FokI, BsmI, ApaI, and TaqI recognizing polymorphic sites in the VDR locus. Bone mineral density was measured at the lumbar spine and at the hip by dual-energy X-ray absorptiometry (DEXA, g/cm2). After adjusting for age and the body mass index (BMI), subjects with the ff genotype had 9.4% lower BMD at the hip than those with the Ff genotype (p=0.0459, Tukey's test). FF individuals had an intermediate BMD at the hip. A similar pattern of lower lumbar spine BMD was also found in ff individuals, but it did not reach statistical significance. There was no relationship between BsmI, ApaI and TaqI VDR polymorphisms and BMD at any skeletal site. Subjects with Aa (ApaI) genotypes had higher levels of propeptide of type I collagen (PICP) than homozygous AA (p=0.0459, Tukey's test). In FokI, BsmI and TaqI restriction sites the biochemical markers of bone remodeling did not differ by genotype. In addition, no significant difference was observed in VDR genotypic distribution between osteoporotic women and non-osteoporotic controls in the study group. To conclude, the FokI genotype of the vitamin D receptor gene is related to bone mass at the hip in Czech postmenopausal women, whereas the importance of remaining VDR genotypes was not evident.     

Vitamin D receptor gene polymorphisms and susceptibility of hand osteoarthritis in Finnish women

We examined whether polymorphisms of the vitamin D receptor (VDR) gene was associated with individual risk of hand osteoarthritis (OA). Radiographs of both hands of 295 dentists and of 248 teachers were examined and classified for the presence of OA using reference images. The VDR ApaI and TaqI genotypes were determined by PCR-based methods. No association was observed between the VDR polymorphisms and the odds of overall hand OA. However, the carriers of the VDR t allele or At haplotype were at almost half the odds of symmetrical hand OA (odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.38–0.94 and OR = 0.59, 95% CI = 0.38–0.93, respectively) compared with the carriers of the T allele and of the non-At haplotype, respectively. Increased odds of this disease, on the contrary, was observed for women with two copies of the VDR a allele (OR = 1.93, 95% CI = 1.99–3.70) compared with women with the AA genotype. Conversely, the VDR a allele carriage was associated with a tendency of lowered odds of osteophyte (OR = 0.51, 95% CI = 0.25–1.03). When the genotype data were used to construct haplotypes, the VDR AaTt joint genotype appeared to pose a remarkably lower odds (OR = 0.26, 95% CI = 0.08–0.91) of osteophyte compared with the AAtt joint genotype. As a novel finding we observed a joint effect of a low calcium intake and VDR polymorphisms on symmetrical OA; the OR was 2.64 (95% CI = 1.29–5.40) for carriers of the aT haplotype with low daily calcium intake compared with non-carriers of the haplotype with high daily calcium intake. Our results suggest that VDR gene polymorphisms play a role in the etiology of symmetrical hand OA. Moreover, the association between the VDR gene and OA may be modified by calcium intake.     

Vitamin D receptor gene polymorphisms and susceptibility of hand osteoarthritis in Finnish women

We examined whether polymorphisms of the vitamin D receptor (VDR) gene was associated with individual risk of hand osteoarthritis (OA). Radiographs of both hands of 295 dentists and of 248 teachers were examined and classified for the presence of OA using reference images. The VDR ApaI and TaqI genotypes were determined by PCR-based methods. No association was observed between the VDR polymorphisms and the odds of overall hand OA. However, the carriers of the VDR t allele or At haplotype were at almost half the odds of symmetrical hand OA (odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.38-0.94 and OR = 0.59, 95% CI = 0.38-0.93, respectively) compared with the carriers of the T allele and of the non-At haplotype, respectively. Increased odds of this disease, on the contrary, was observed for women with two copies of the VDR a allele (OR = 1.93, 95% CI = 1.99-3.70) compared with women with the AA genotype. Conversely, the VDR a allele carriage was associated with a tendency of lowered odds of osteophyte (OR = 0.51, 95% CI = 0.25-1.03). When the genotype data were used to construct haplotypes, the VDR AaTt joint genotype appeared to pose a remarkably lower odds (OR = 0.26, 95% CI = 0.08-0.91) of osteophyte compared with the AAtt joint genotype. As a novel finding we observed a joint effect of a low calcium intake and VDR polymorphisms on symmetrical OA; the OR was 2.64 (95% CI = 1.29-5.40) for carriers of the aT haplotype with low daily calcium intake compared with non-carriers of the haplotype with high daily calcium intake. Our results suggest that VDR gene polymorphisms play a role in the etiology of symmetrical hand OA. Moreover, the association between the VDR gene and OA may be modified by calcium intake.     

Vitamin D Receptor Gene Expression and Function in a South African Population: Ethnicity,Vitamin D and FokI

Polymorphisms of the vitamin D receptor gene (VDR) have been associated inconsistently with various diseases, across populations of diverse origin. The T(f) allele of the functional SNP FokI, in exon 2 of VDR, results in a longer vitamin D receptor protein (VDR) isoform, proposed to be less active. Genetic association of VDR with disease is likely confounded by ethnicity and environmental factors such as plasma 25(OH)D₃ status. We hypothesized that VDR expression, VDR level and transactivation of target genes, CAMP and CYP24A1, depend on vitamin D, ethnicity and FokI genotype. Healthy volunteers participated in the study (African, n = 40 and White, n = 20). Plasma 25(OH)D₃ levels were quantified by LC-MS and monocytes cultured, with or without 1,25(OH)₂D₃. Gene expression and protein level was quantified using qRT-PCR and flow cytometry, respectively. Mean plasma 25(OH)D₃ status was normal and not significantly different between ethnicities. Neither 25(OH)D₃ status nor 1,25(OH)₂D₃ supplementation significantly influenced expression or level of VDR. Africans had significantly higher mean VDR protein levels (P<0.050), nonetheless transactivated less CAMP expression than Whites. Genotyping the FokI polymorphism by pyrosequencing together with HapMap data, showed a significantly higher (P<0.050) frequency of the CC genotype in Africans than in Whites. FokI genotype, however, did not influence VDR expression or VDR level, but influenced overall transactivation of CAMP and 1,25(OH)₂D₃-elicited CYP24A1 induction; the latter, interacting with ethnicity. In conclusion, differential VDR expression relates to ethnicity, rather than 25(OH)D₃ status and FokI genotype. Instead, VDR transactivation of CAMP is influenced by FokI genotype and, together with ethnicity, influence 1,25(OH)₂D₃-elicited CYP24A1 expression. Thus, the expression and role of VDR to transactivate target genes is determined not only by genetics, but also by ethnicity and environment involving complex interactions which may confound disease association.     

Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis

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.     

Toll-like receptor polymorphisms and vasculitis susceptibility: meta-analysis and systematic review

The aim of this study was to determine whether toll-like receptor (TLR) polymorphisms confers susceptibility to vasculitis. A literature search was conducted using the PubMed and Embase. A meta-analysis on the associations between the TLR4 Asp299Gly polymorphisms and vasculitis was carried out using allele contrast, dominant, and codominant models and a systematic review of other TLR polymorphisms. Fourteen studies involving 2,064 patients and 2,481 controls were included in this systematic review, which comprised nine on Behcet’s disease (BD), three on giant cell arteritis (GCA), and one on Henoch–Schenlein purpura (HSP). Meta-analysis of six studies showed a significant association between the Gly/Gly+Gly/Asp genotype of the TLR4 Asp299Gly polymorphism and vasculitis and GCA (Odds ratio [OR] = 1.368, 95 % confidence interval [CI] = 1.300–1.815, p = 0.030; OR = 1.523, 95 % CI = 1.099–2.112, p = 0.012). Under a random effects model, the adjusted ORs calculated using the trim and fill technique revealed an association between the Gly/Gly+Gly/Asp genotype of the TLR4 Asp299Gly polymorphism and vasculitis (OR = 1.544, 95 % CI = 1.091–2.185, p < 0.05). Stratification by vasculitis type using the codominant model showed the trend for the association with GCA (OR = 1.569, 95 % CI = 0.970–2.538, p = 0.066). There were three studies on the TLR2 Arg753Gln polymorphism and two on the TLR4 Thr399Ile polymorphism; no association with vasculitis was evident. Among the TLR2, TLR7, and TLR9 polymorphisms included in this review, one Asian study revealed a significant association between the TLR7 rs5743733 and rs3853839 with BD (p = 0.002, 0.036) and one Asian study showed an association of TLR9 rs352140 with BD (p = 0.009). This meta-analysis demonstrates that the TLR4 Asp299Gly polymorphism may confer susceptibility to GCA. The review of published data suggests that other TLR polymorphisms such as TLR7 and TLR9 may play a role in vasculitis.     

Associations between interleukin-23 receptor polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis

The aim of this study was to determine whether interleukin-23 receptor (IL-23R) polymorphisms confer susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the IL-23R rs1343151, rs10489629, rs7517847, rs11209026, rs1004819, and rs2201841 polymorphisms and RA using (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 13 studies from eight articles involving 10,016 RA patients and 11,967 controls were considered in the meta-analysis. Meta-analysis identified a significant association between RA and the A allele of the rs1343151 polymorphism in the overall population (OR?=?1.110, 95?% CI?=?1.056–1.168, p?=?4.7?×?10^?6). Stratification by ethnicity identified a significant association between this polymorphism and RA in Europeans (OR?=?1.105, 95?% CI?=?1.049–1.163, p?=?1.4?×?10^?5). An association was also found between RA and the A allele carrier of the rs1343151 polymorphism in Europeans (OR?=?1.135, 95?% CI?=?1.058–1.217, p?=?4.0?×?10^?5). Meta-analysis revealed a significant association between RA and the A allele of the rs10489629 polymorphism in the overall population (OR?=?1.079, 95?% CI?=?1.029–1.131, p?=?0.002) and in Europeans (OR?=?1.092, 95?% CI?=?1.038–1.149, p?=?0.001). Meta-analyses of recessive, dominant, and additive models showed the same pattern as the meta-analysis of the A allele of the rs10489629 polymorphism, that is, a significant association with RA in Europeans. However, no association was found between the IL-23R rs7517847, rs11209026, rs1004819, and rs2201841 polymorphisms and RA susceptibility. This meta-analysis shows that the IL-23R rs1343151 and rs10489629 polymorphisms are associated with the development of RA in Europeans. These findings suggest that the IL-23R genes confer susceptibility to RA in the European population, but further study of this association is required in other ethnic groups.     

Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children

Background

Type 1 diabetes mellitus (T1DM) is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to suppress T-cell activation by binding to vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. The aim of this study was to investigate the association between vitamin D status and VDR gene polymorphisms and T1DM.

Materials and methods

One hundred and twenty patients with T1DM and one hundred and twenty controls were enrolled in the study. VDR gene BsmI, FokI, ApaI and TaqI polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum 25-hydroxyvitamin D (25(OH)D) was determined using ELISA.

Result

Serum 25(OH)D levels revealed a vitamin D deficiency or insufficiency in 75% of the patients. The mean levels of vitamin D were significantly lower in patients as compared to their controls (P = < 0.001). VDR BsmI Bb and bb genotypes and VDR FokI Ff and ff genotypes were associated with increased risk of T1DM (OR = 2.3, 95% CI = 1.3–4.2, P = 0.005; OR = 2.2, 95% CI = 1.1–4.7, P = 0.04; OR = 1.8, 95% CI = 1.03–3.04, P = 0.04; OR = 4.03, 95% CI = 1.2–13.1, P = 0.01 respectively), while the VDR ApaI and TaqI polymorphisms were not.

Conclusion

Our study indicated that vitamin D deficiency and VDR BsmI and FokI polymorphisms were associated with T1DM in Egyptian children.