Association between vitamin D receptor gene haplotypes and chronic periodontitis among Japanese men

BACKGROUND: The vitamin D receptor (VDR) is involved in a variety of biological processes, such as bone metabolism and modulation of the immune response. Recent findings suggest that the pathway involving bone mineral density-mediated effects is important for the development of periodontitis, but their effects of combined VDR gene polymorphisms have not been confirmed on periodontitis. We assessed the relationship between ApaI, BsmI, and FokI VDR polymorphisms and the risk of severe chronic periodontitis among Japanese adult men. MATERIALS AND METHODS: In a cross-sectional study, we examined 97 unrelated healthy Japanese men (mean age: 45.6 years, range: 22-59). A clinical examination was performed at a worksite health checkup, and information was obtained using a self-reported questionnaire. DNA was extracted from whole blood, and the VDR ApaI, BsmI, and FokI polymorphisms were genotyped using polymerase chain reaction. RESULTS: F-carriers of FokI VDR polymorphisms were less likely to develop severe chronic periodontitis than non-F-carriers (p = 0.09). The ApaI and BsmI VDR polymorphisms did not show significant differences in the alleles or genotypes between the subjects with or without severe chronic periodontitis. The haplotype analysis of the three combined VDR polymorphisms revealed that the Abf homozygote had a notably higher prevalence of severe chronic periodontitis than the others, and adjustments for age, smoking status, number of teeth present, and prevalence of diabetes did not change this association (OR = 7.5; 95% CI = 1.6-34.4; p = 0.01). CONCLUSION: The VDR haplotype constructed from the ApaI, BsmI, and FokI polymorphisms is related to the risk of severe chronic periodontitis in Japanese men.     

BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and the risk of osteoporosis: a meta-analysis

A meta-analysis regarding BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and their associations with osteoporosis in females is reported. The meta-analysis involved 14, seven, seven and three studies for BsmI, TaqI, ApaI and FokI polymorphisms, respectively. The studies were association studies with osteoporotic cases and controls free of osteoporosis that provided the genotype distribution of individual cases and controls. For the BsmI polymorphism, the allele contrast b vs. B showed heterogeneity among studies (p< 0.01, I2> 50%) and the random effects (RE) pooled odds ratio (OR) was non-significant: 0.94 [95% confidence interval (CI) 0.63-1.38]. Caucasians, postmenopausal cases and studies with WHO diagnostic criteria showed no association under any genetic contrast. However, in East Asians, the OR for the dominant model [fixed effects OR=0.14 (95% CI 0.04-0.50) and RE OR=0.16 (95% CI 0.03-0.84)] was significant, indicating prevention. Overall, for the TaqI, ApaI and FokI polymorphisms, the allele contrast showed heterogeneity and the pooled RE ORs were non-significant [OR=1.06 (95% CI 0.71-1.60), OR=0.99 (95% CI 0.72-1.37) and OR=1.17 (95% CI 0.76-1.80), respectively]. The allele contrast for Caucasians, East Asians, postmenopausal cases and studies with WHO diagnostic criteria showed no association for TaqI, ApaI, and FokI. The allele contrast of homozygotes, and the recessive and dominant models the results followed the same pattern as the allele contrast. Therefore, the relationship between the VDR polymorphisms and osteoporosis remains an unresolved issue and other probable genetic-environmental risk factors interacting with the above polymorphisms should be investigated.     

Vitamin D receptor gene polymorphism and its association with Parkinson's disease in Chinese Han population

Vitamin D plays an important role in neurodegenerative disorders as a crucial neuro-immunomodulator, and accumulating data have provided evidence for that vitamin D receptor (VDR) gene is a candidate gene for susceptibility to Parkinson's disease (PD). In this study, we performed a case-control study to demonstrate whether the risk for the development of onset of sporadic PD might be influenced by VDR gene polymorphisms in a Chinese cohort. Two hundred and sixty PD patients and 282 matched-healthy controls were genotyped for two representative single nucleotide polymorphisms (SNPs) in VDR gene (FokI C/T and BsmI G/A) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis in. Results from our study revealed that FokI C allele carriers were likely to associate with an increased risk of PD (P = 0.004) as well as early-onset PD (EOPD) (P = 0.010). Moreover, the frequency of FokI C allele was significantly increased in PD group and late-onset PD (LOPD) group relative to the control groups respectively (P = 0.023 and P = 0.033, respectively). For BsmI polymorphisms, no significant difference in genotype or allele distribution was found between PD patients and the controls, as well as gender- and age-related differences between PD patients and the controls subgroup. This study demonstrated a possible association between the VDR FokI T/C polymorphism and PD, indicating that VDR polymorphisms may well change genetic susceptibility to sporadic PD in a Han Chinese population.     

Polymorphisms in the vitamin D receptor and their associations with risk of schizophrenia and selected anthropometric measures.

The association between vitamin D levels and skeletal growth has long been recognized. However, exposure to low levels of vitamin D during early life is also known to alter brain development, and is a candidate risk factor for schizophrenia. This study examines the association between four polymorphisms in the vitamin D receptor (VDR) and 1) risk of schizophrenia, and 2) three anthropometric variables (height, head size, and head shape). Four single-nucleotide polymorphisms (SNPs; rs10735810/FokI, rs1544410/BsmI, rs7975232/ApaI, and rs731236/TaqI) in the VDR gene were genotyped in 179 individuals with schizophrenia and 189 healthy controls. No significant associations were detected between any of the four VDR SNPs and risk of schizophrenia. Patients were slightly but significantly shorter compared to controls. Of the four SNPs, only rs10735810/FokI was associated with any of the anthropometric measures: the M4 isoform of this SNP was significantly associated with larger head size (P = 0.002). In light of the evidence demonstrating a role for vitamin D during brain development, the association between polymorphisms in VDR and brain development warrants closer scrutiny.     

Serum 25-Hydroxy Vitamin D Levels and Association of Vitamin D Receptor Gene Polymorphisms in Vitiligo

BackgroundThe role of vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms has been established in many autoimmune diseases, including vitiligo, but the result is still controversial.ObjectivesThe aim of this study was to investigate the serum vitamin D levels in vitiligo patients and to compare the association of VDR gene polymorphisms in vitiligo patients and healthy controls.MethodsWe collected the data of age, sex, serum 25-hydroxy vitamin D (25[OH]D) level, thyroid autoantibodies, disease duration, types of vitiligo, family history and the affected body surface area of vitiligo from 172 patients. And we analyzed the VDR gene polymorphisms in 130 vitiligo and 453 age-sex-matched control subjects.ResultsThe mean serum level of 25(OH)D in 172 vitiligo patients was 18.75 ± 0.60 ng/mL, which had no significant difference with a mean serum value of 25(OH)D in the Korean population. However, there were significant differences according to the duration of the disease and family history. Also, there were no significant differences in the genotypic and allelic distributions of 37 examined SNPs of VDR gene between vitiligo patients and healthy controls.ConclusionSerum level of 25(OH)D in vitiligo patients was not significantly different from the mean serum value of the Korean population. Also, there were no significant differences in the genotypic distributions of VDR gene between vitiligo patients and healthy controls.     

Association study of VDR gene with rheumatoid arthritis in the French population

Vitamin D is a potent regulator of calcium homeostasis and may have immunomodulatory effects. The influence of vitamin D on human autoimmune disease is controversial. The aim of this study was to investigate the role of vitamin D receptor gene (VDR) in rheumatoid arthritis (RA). Three polymorphisms for VDR gene FokI T>C (rs 10735810), BsmI A>G (rs 1544410) and TaqI C>T (rs 731236) were genotyped in 100 RA French nuclear families (set 1) and 100 additional French nuclear families for replication (set 2). The association analysis was performed using comparison of alleles frequencies (AFBAC), transmission disequilibrium test and genotype relative risk. Our results revealed a significant difference of F allele of FokI polymorphism between transmitted and nontransmitted frequencies (P=0.01) in set 1. Furthermore, the F/F genotype was more frequent in RA patients compared to controls (P=0.01) in set 1. The replication in set 2 showed similar patterns of transmission with a nonsignificant association. Association with FokI was found to be significant when the two sets were combined (P=0.006). These data suggest that the F allele and F/F VDR genotype are associated with RA. The mechanisms by which distinct receptor variants might confer disease susceptibility remain to be elucidated.     

VDR gene variants associate with cognitive function and depressive symptoms in old age

Vitamin D has been recently implicated in brain function. Our objective was to test whether genetic variance in the vitamin D receptor (VDR) gene is associated with cognitive functioning and depressive symptoms in old age. The study was carried out in the prospective population-based Leiden 85-plus Study. All 563 participants of the study were genotyped for Cdx-2, FokI, BsmI, ApaI and TaqI polymorphisms in the VDR gene. Our data revealed an overall worse performance on tests measuring cognitive functioning for carriers of BsmI (p=0.013) and TaqI (p=0.004) polymorphisms, and of haplotype 2 (BAt) (p=0.004). In contrast, carriers of ApaI variant-allele and of haplotype 1 (baT) had better cognitive functioning together with less depressive symptoms. These associations could not be explained by differences in calcium levels, and by selective survival, since no associations between the VDR gene variants and calcium levels and mortality were observed. In conclusion, our results show that genetic variance in the VDR gene influences the susceptibility to age-related changes in cognitive functioning and in depressive symptoms.     

Lack of association of vitamin D receptor gene polymorphisms with susceptibility to type 1 diabetes mellitus in the Portuguese population

The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. Association studies of VDR polymorphisms and risk of type 1 diabetes often produced conflicting results in different ethnic backgrounds. The aim of this study was to test for association between common VDR polymorphisms and the genetic susceptibility to type 1 diabetes in the Portuguese population. We genotyped 207 patients with type 1 diabetes and 249 controls for the FokI T>C (rs10735810), BsmI A>G (rs1544410), ApaI G>T (rs7975232), and TaqI C>T (rs731236) single nucleotide polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. The distribution of VDR genotype, allele, and haplotype frequencies did not differ significantly between patients and controls. These data suggest that the single nucleotide polymorphisms of the VDR gene are unlikely to contribute significantly to type 1 diabetes susceptibility in the Portuguese population.     

Association of polymorphisms in the vitamin D receptor gene with susceptibility to and severity of hand,foot, and mouth disease caused by coxsackievirus A16

Coxsackievirus A16 (CA16) remains the most common causative agent of hand, foot, and mouth disease (HFMD), and is related to high incidence and critical complications. Vitamin D receptor (VDR) activity might affect the outcome of CA16 infection. Our case-control research aims to evaluate the relationship between VDR polymorphisms in the gene encoding and susceptibility to and severity of HFMD due to CA16. Three single-nucleotide polymorphisms (SNPs) of VDR gene were selected according to functional prediction and linkage disequilibrium, and were examined utilizing the SNPscan method to identify possible associations with HFMD caused by CA16. A significant relationship was found in the HFMD cases of polymorphism rs11574129 (GA vs GG: odds ratio (OR) = 0.068, 95% confidence interval (CI) = 0.007-0.693, P = .023; GA + AA vs GG: OR = 0.322, 95%CI = 0.106-0.984, P = .047), and vitamin D levels in genotype AA were significantly higher than those in genotype GG (P < .05). These results suggest that VDR rs11574129 may influence genetic susceptibility to CA16-associated HFMD.     

The role of vitamin D receptor gene polymorphisms in the susceptibility to prostate cancer of a southern European population

 Epidemiological data indicate a relationship between ultraviolet radiation, vitamin D, and prostate cancer risk. Antiproliferative effects of vitamin D require the expression of the nuclear vitamin D receptor (VDR). A three-fold increase in prostate cancer risk associated with the less active vitamin D receptor allele (the T allele from VDR TaqI polymorphism at codon 352) was reported. The role of VDR genotypes in the susceptibility to prostate cancer has not yet been studied in populations of southern Europe. In the present study, we determined VDR TaqI genotypes in Portuguese prostate cancer cases (n= 163) and controls (n= 211), a southern European population. When cases were compared with controls, we found an association of VDR T allele with prostate cancer risk (odds ratio [OR] = 1.87, 95% confidence interval [CI] 1.02–3.37; P= 0.035). This association was confirmed using logistic regression analysis (OR = 2.11, 95% CI 1.15–3.88; P= 0.015) and in particular associated to risk of prostate cancer onset in men over the age of 66 years (OR = 2.36, 95% CI 1.05–5.29; P= 0.036). Fifty percent of cases older than 66 years could be attributed to the influence of this risk factor. Our results indicate that the contribution of VDR genotypes to prostate cancer susceptibility might depend on the population studied and its geographic localization, and that VDR genotypes are important in the definition of the genetic risk profile of populations of southern Europe. Received: March 13, 2002 / Accepted: March 25, 2002     

Vitamin D receptor gene polymorphisms and bone mineral density in postmenopausal Indian women

OBJECTIVES: Osteoporosis is a common condition in postmenopausal women. Bone mineral density (BMD), the major determinant of osteoporotic fracture risk, has a particular genetic background. However, consensus on the association of BMD with specific gene locus has not been reached. The race and ethnicity specific divergence in association studies must be assessed to predict the susceptibility and therapeutic response of associated genes. We investigated the potential association of Vitamin D receptor (VDR) gene polymorphisms ApaI, BsmI, FokI and TaqI with BMD in 246 postmenopausal Indian women (average age 54.2+/-3.4 years). METHODS: The subjects were genotyped by PCR-RFLP and underwent BMD measurements at spine and hip by dual energy X-ray absorptiometery. RESULTS: The average BMD at spine and hip of women with genotypes aa, bb (presence of restriction sites for ApaI and BsmI), FF and TT (absence of restriction sites for FokI and TaqI) was more than 10% higher than those with genotypes AA, BB, ff and tt, respectively. The interaction between BsmI, ApaI and TaqI genotypes showed significant effect of BsmI-ApaI genotypes (p=0.052) in this combination on BMD. However, presence of T allele in combination showed positive influence on BMD. Within the group, genotypes BB, ff and tt were significantly prevalent in women with osteoporotic bone mass, tt and BB had significantly higher adjusted odd ratio (OR) for age more than 55years. CONCLUSION: Study reveals that VDR gene polymorphisms are associated with BMD in Indian women and perhaps, influence some determinant of bone metabolism. Ethnicity may attribute to frequency variation, however, allele impact remains same.     

Vitamin D and autoimmune thyroid diseases

The role of vitamin D as an immune modulator has been emphasized in recent years, and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus erythematosus. Vitamin D mediates its effect though binding to vitamin D receptor (VDR), and activation of VDR-responsive genes. While VDR gene polymorphism was found to associate with autoimmune thyroid diseases (AITDs), few studies examined levels of vitamin D in these patients and those that did yielded conflicting results. We therefore undertook to evaluate the levels of vitamin D in patients with AITDs compared to patients with non-AITDs and healthy controls. Serum vitamin D (25-OH) levels were measured in 50 patients with AITDs, 42 patients with non-AITDs and 98 healthy subjects, utilizing the LIAISON chemiluminescence immunoassay (DiaSorin, Saluggia, Italy). Vitamin D deficiency was designated at levels lower than 10 ng/ml. Antithyroid antibodies, thyroid functions and demographic parameters were evaluated in all patients. The prevalence of vitamin D deficiency was significantly higher in patients with AITDs compared with healthy individuals (72% versus 30.6% P<0.001), as well as in patients with Hashimoto''s thyroiditis compared to patients with non-AITDs (79% versus 52% P<0.05). Vitamin D deficiency also correlated to the presence of antithyroid antibodies (P=0.01) and abnormal thyroid function tests (P=0.059). Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests, suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.     

Vitamin D receptor FokI genotype influences bone mineral density response to strength training, but not aerobic training

To determine the influence of the vitamin D receptor (VDR) gene FokI and BsmI genotype on bone mineral density response to two exercise training modalities, 206 healthy men and women (50-81 years old) were studied before and after approximately 5-6 months of either aerobic exercise training (AT) or strength training (ST). A totla of 123 subjects completed AT (51 men, 72 women) and 83 subjects completed ST (40 men, 43 women). DNA was extracted from blood samples of all subjects and genotyping was performed at the VDR FokI and BsmI locus to determine its association to training response. Total body, greater trochanter and femoral neck bone mineral density (BMD) were measured before and after both training programmes using dual-energy X-ray absorptiometry. VDR BsmI genotype was not significantly related to BMD at baseline or after ST or AT. However, VDR FokI genotype was significantly related to ST- but not AT-induced changes in femoral neck BMD (P < 0.05). The heterozygotes (Ff) in the ST group approached a significantly greater increase in femoral neck BMD (P = 0.058) compared to f homozygotes. There were no significant genotype relationships in the AT group. These data indicate that VDR FokI genotype may influence femoral neck BMD response to ST, but not AT.     

The association between serum 25-hydroxyvitamin D concentrations and serum lipids in the Southern Thai population

IntroductionDyslipidaemia is a major risk factor for cardiovascular diseases (CVD). Vitamin D deficiency has been found to be associated with CVD. However, the relationships between vitamin D and lipids are inconsistent. The aim of this study was to investigate the relationship between vitamin D status and serum lipids in Southern Thai subjects.Material and methodsA total of 726 healthy subjects in Southern Thailand were enrolled in the study. Serum 25-hydroxyvitamin D (25(OH)D), lipid profiles, fasting plasma glucose, anthropometric data, blood pressure, and body composition were measured. The relationship between serum 25(OH)D levels and biochemical data was evaluated by partial correlation and multiple linear regression analyses. The association of serum 25(OH)D levels with dyslipidaemia was analysed using multivariate regression analysis.ResultsSerum 25(OH)D levels were negatively correlated with body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and body composition parameters after adjusting for age in women. Multiple linear regression analysis showed that TC and BMI were independent predictors for 25(OH)D concentrations in women. Multivariate logistic regression analysis showed that the odds ratio of hypertriglyceridaemia (OR = 0.51; 95% CI: 0.32–0.80, p = 0.004) and reduced high-density lipoprotein cholesterol (HDL-C) (OR = 0.43; 95% CI: 0.26–0.71, p = 0.001) were significantly lower in vitamin D sufficiency when compared with hypovitaminosis D in women.ConclusionsVitamin D sufficiency could reduce risk of hypertriglyceridaemia and reduced HDL-C, particularly in women, suggesting that vitamin D sufficiency may have beneficial effects on lipids and a decreased risk for CVD in Thai women.     

Vitamin D receptor gene polymorphisms association with the risk of sepsis and mortality

Association of vitamin D receptor (VDR) gene polymorphisms with sepsis risk and mortality was studied. VDR FokI CC genotype was associated with increased sepsis risk (OR = 13.396, p = .000009) compared to the TT genotype. Results suggest possible role of VDR FokI (rs2228570) as a molecular biomarker of increased sepsis risk.     

Associations between vitamin D receptor polymorphisms and susceptibility to Behcet’s disease: A meta-analysis

Background: The vitamin D receptor (VDR) gene polymorphisms have been reported to be related to the development of Behcet’s disease (BD). However, the results have been inconsistent among diverse populations. Therefore, this comprehensive meta-analysis has been designed to assess a more accurate association between VDR polymorphisms and BD susceptibility.

Methods: An electronic literature search was conducted to identify eligible studies. Pooled odds ratios (OR) with corresponding 95% confidence interval (CI) were calculated in different genetic models to assess this association.

Results: A total of six separate comparisons comprised of 468 cases and 516 controls were included in the meta-analysis model. The meta-result demonstrated that A allele of ApaI (A vs. a: 1.54 95% CI = 1.04–2.26, P = 0.029), and F allele of FokI (F vs. f: OR = 0.58, 95% CI = 0.45–0.76, P = 0.007) polymorphisms were associated with the risk of BD in total and African populations, respectively. This significant association was also found in recessive and homozygotes models. Subgroup analysis indicated that FokI variant among Africans and ApaI variant among Caucasian were significantly associated with the risk of BD. No relationship was found between Bsmi and TaqI polymorphisms and BD risk.

Conclusion: This meta-analysis demonstrated the association between FokI and ApaI polymorphisms in VDR gene with the risk of BD, providing insights into the potential role of vitamin D receptor in the pathogenesis of BD.     

Heterogeneity of vitamin D receptor gene association with celiac disease and type 1 diabetes mellitus

Objective: Vitamin D has been shown to exert multiple immunomodulatory effects and is known to suppress T-cell activation by binding to the vitamin D receptor (VDR). To determine whether VDR gene polymorphisms are related to the susceptibility to celiac disease, we investigated its implication as a candidate gene in the Basque population. Because celiac disease and type 1 diabetes share common susceptibility loci, we also analyzed families with type 1 diabetes mellitus.

Methods: A total of 37 families with celiac disease and 64 type 1 diabetic families of Basque origin with at least one affected offspring were genotyped for four VDR restriction-site polymorphisms (Fok I, Bsm I, Apa I and Taq I). The AFBAC approach was used to test for association.

Results: Comparison of VDR genotypes of the patients with those of 88 healthy individuals identified “ff” as a risk genotype for celiac disease [p = 0.01; OR = 3.45 (1.12–10.79)]. On the other hand, a significantly higher frequency of haplotype “fBAt” was observed in the type 1 diabetic group [p_c = 0.02; OR = 4.4 (1.5–15.3)].

Conclusion: Our findings suggest that polymorphisms within the vitamin D receptor gene are markers of susceptibility to or protection from autoimmune diseases, although, at least in the Basque population, association of VDR variants with celiac disease and type 1 diabetes seems to be heterogeneous.     

Association of VDR ApaI and TaqI Gene Polymorphisms with the Risk of Scleroderma and Behçet’s Disease

Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms have been reported in autoimmune diseases. However, their role in Behçet’s disease (BD) and scleroderma remains inconclusive. Our aim was to evaluate vitamin D receptor (ApaI, TaqI) gene polymorphisms in relation to Behçet’s disease and scleroderma in Egyptians. The study was conducted on 54 patients with BD, 30 scleroderma patients, and 60 healthy control subjects. VDR (ApaI, TaqI) gene polymorphisms were investigated using polymerase chain reaction-restriction fragment length polymorphism technique. The “a” allele of ApaI (A/a) polymorphism was significantly associated with increased BD risk (OR = 2.09, 95% CI = 1.18–3.71, p = 0.011), while the TaqI “tt” genotype was significantly lower in BD patients as compared to control subjects (OR = 0.35, 95% CI = 0.13–0.9, p = 0.026). Carriage of “aT” VDR haplotype was significantly associated with higher BD risk (OR = 2.28, 95% = 1.14–4.56, p = 0.022). In conclusion, our findings suggest that VDR gene polymorphisms have a significant association with BD in Egyptian patients.