Association of vitamin D receptor genotypes with early onset rheumatoid arthritis.

The presence of certain vitamin D receptor (VDR) genotypes has been associated with low bone mineral density (BMD) in elderly populations as well as with accelerated bone loss in patients with rheumatoid arthritis (RA). In the present study, VDR genotypes from 120 Spanish patients with RA were investigated. Three VDR gene polymorphisms (BsmI, ApaI and TaqI) were investigated using polymerase chain reaction followed by enzymatic digestion. The distributions of VDR allelic frequencies were similar in patients and controls and therefore no influence of VDR polymorphisms on rheumatoid arthritis susceptibility could be demonstrated. However, in an analysis of the clinical features of the different VDR-related genetic subgroups, the BB/tt genotype, defined by the BsmI and TaqI restriction site polymorphisms, was identified to be weakly associated with an early onset RA in female patients. This VDR genotype has been associated with a low BMD level in various studies. When patients were stratified according to the presence of the shared HLA epitope SE, it was found that SE + female patients bearing the BB/tt genotype showed the earliest disease onset. The mechanisms by which the VDR polymorphism is associated with RA is unknown, but they could be related to the immunoregulatory properties of vitamin D.     

Lack of relationship between vitamin D receptor polymorphism and bone erosion in rheumatoid arthritis

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.     

Vitamin D receptor gene polymorphism as possible risk factor in rheumatoid arthritis and rheumatoid related osteoporosis

Objective

To study the role of VDR polymorphisms as risk factor for RA and osteoporosis, and whether osteoporosis complicating RA is due to RA or VDR polymorphisms.

Methods

VDR gene polymorphisms ApaI, TaqI, BsmI and FokI were typed by RFLP for 128 RA patients, 30 postmenopausal osteoporotic females and 150 healthy controls.

Results

Significant differences were found between patients and healthy controls in the frequency of BsmI and TaqI (Pc < 0.05) but no significant associations were found for FokI and ApaI polymorphisms except for aa genotype (Pc < 0.001). Titers of RF were higher with aa and bb genotypes. Anti-CCP and CRP levels were higher with aa genotype and more bone loss was associated with Bb genotype. Ff genotype frequency was higher in RA patients with osteoporosis than those without osteoporosis.

Conclusions

The ApaI, BsmI and TaqI polymorphisms may be a susceptibility risk factors for RA and the Ff genotype may be responsible for development of osteoporosis in RA Egyptian patients. However, the present study needs to be replicated in a large number of patients from allover the Egypt and also in multi-ethnic populations.     

Age‐ and gender‐specific effects on VDR gene polymorphisms and risk of the development of multiple sclerosis in Tunisians: a preliminary study

The vitamin D receptor (VDR) polymorphisms have been reported to be associated with multiple sclerosis (MS); however, evidence remains conflicting. In this report, we investigated the association between two single nucleotide polymorphisms (SNPs) TaqI and ApaI of VDR gene and risk development of MS. TaqI and ApaI SNPs were detected by PCR‐RFLP from the DNA of 60 Tunisian patients with MS and 114 healthy controls. Our results show a significant difference of the allelic frequency distribution between the case and control groups for TaqI SNP (P = 0.01), but genotype frequencies were not significantly different (P = 0.07 and 0.23). When adjusting frequency distribution of different alleles and genotypes by age, we found that the difference between the T allele frequencies of this SNP in the group of patients age [15?24] in comparison with the control group of the same age group was statistically significant (P = 0.026). Moreover, frequency of the T allele was significantly higher in male patients compared with controls of the same sex (P = 0.017). However, neither the genotype nor the allele frequency distribution was significantly different between the MS and control populations for the ApaI SNP. Our preliminary results indicate that VDR gene polymorphism could be associated with susceptibility to MS. The role of VDR gene polymorphism should be further studied in other large populations, and the distribution of other polymorphism, such as FokI and BsmI, should be also analysed to confirm another susceptibility polymorphisms gene for MS and to obtain more adequate strategies for treatment of MS.     

Vitamin D receptor polymorphisms and bone mineral density in Mexican women without osteoporosis

Polymorphisms corresponding to Apa I, Bsm I, and Taq I restriction endonucleases at the vitamin D receptor (VDR) gene and bone mineral density (BMD) at lumbar spine (L2–L4) and proximal femur (neck, Ward's triangle and trochanteric region) sites were examined in a sample of 98 Mexican women (age 55 ± 10 years). None of the subjects were pregnant or nursing and none had a previous diagnosis of osteoporosis. Polymorphisms were assessed by the restriction fragment length polymorphism − polymerase chain reaction (RFLP-PCR) technique. Alleles were denoted with capital letters for the absence of the RFLP site (A, B, or T) and with small letters for its presence (a, b, or t). BMD was assessed by dual energy X-ray absorptiometry (DXA). A structured, self-administrated questionnaire was used to obtain data on age, menopause, number of pregnancies, breast-feeding, fractures, exercise, smoking, alcohol, estrogens, calcium supplement, height, weight, and BMI. There were no differences between BMD at the skeletal sites and the genotypes disclosed by Apa I (Allele A = 0.43), Bsm I (Allele B = 0.26) and Taq I (Allele T = 0.76). The present study provides data for comparison with other studies to determine the possible value of genotyping VDR to predict predisposition for osteoporosis in Mexican or Mexican-American women. Am. J. Hum. Biol. 11:793–797, 1999. © 1999 Wiley-Liss, Inc.     

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.     

Regulatory Role of Vitamin D Receptor Gene Variants of BsmI, ApaI, TaqI, and FokI Polymorphisms on Macrophage Phagocytosis and Lymphoproliferative Response to Mycobacterium tuberculosis Antigen in Pulmonary Tuberculosis

The regulatory role of vitamin D receptor (VDR) gene variants of Bsm I, Apa I, Taq I, and Fok I polymorphisms on vitamin D(3)-modulated macrophage phagocytosis with live Mycobacterium tuberculosis and lymphoproliferative response to M. tuberculosis culture filtrate antigen (CFA) was studied in patients with pulmonary tuberculosis (n = 46) and in normal healthy subjects (NHS) (n = 64). Vitamin D(3) at a concentration of 1 x 10(-7) M enhanced the phagocytic potential of normal subjects who had a phagocytic index of less than 20%. This increase was seen in subjects with the genotypes BB (p = 0.017), AA (p = 0.016), tt (p = 0.034), and FF (p = 0.013) and the extended genotype BBAAtt (p = 0.034). Normal subjects with BBAAtt performed better phagocytosis than individuals with bbaaTT genotype (p = 0.034). Vitamin D(3) at 10(-9), 10(-8), and 10(-7) M concentrations suppressed the lymphoproliferative response to CFA antigen in normal subjects. This decreased lymphocyte response was observed in normal individuals with the genotypes BB (p = 0.0009), tt (p = 0.016), and FF (p = 0.008) and the extended genotype BBAAtt (p = 0.02). Addition of vitamin D(3) had no significant effect on macrophage phagocytosis and lymphoproliferative response to CFA in pulmonary TB patients. This may be due to the unresponsive nature of the cells to the action of vitamin D(3) or the downregulated VDR expression by virtue of the disease, which renders them inactive. The genotypes BB, tt, and the extended genotype BBAAtt may be associated with increased expression of VDR which in turn regulate the action of vitamin D(3) and modulate the immune functions to M. tuberculosis in NHS.     

Plasma 1,25 Dihydroxy Vitamin D<Subscript>3</Subscript> Level and Expression of Vitamin D Receptor and Cathelicidin in Pulmonary Tuberculosis

Introduction  Vitamin D₃, which exerts its effect through vitamin D receptor (VDR), is known for its potent immunomodulatory activities. Associations between low serum vitamin D₃ levels and increased risk of tuberculosis have been reported. Study Subjects and Methods  Plasma 1,25 dihydroxy vitamin D₃ levels (1,25(OH)₂ D₃) and ex vivo levels of VDR protein from peripheral blood mononuclear cells were studied in 65 pulmonary tuberculosis (PTB) patients and 60 normal healthy subjects (NHS) using enzyme-linked immunosorbent assay-based methods. Using real-time polymerase chain reaction (PCR), induction of VDR, cathelicidin, and CYP27B1 mRNA were studied in live Mycobacterium tuberculosis-stimulated macrophage cultures treated with or without 1,25 dihydroxy vitamin D₃. VDR and CYP27B1 (-1077 A/T) gene polymorphisms were studied using PCR-based methods. Results  1,25(OH)₂ D₃ were significantly increased (p = 0.0004), while ex vivo levels of VDR protein were significantly decreased in PTB patients (p = 0.017) as compared to NHS. 1,25(OH)₂ D₃ levels were not different between variant genotypes of CYP27B1. A trend towards decreased levels of VDR protein was observed among NHS with BsmI BB and TaqI tt genotypes compared to NHS with other genotypes. Relative quantification of mRNA using real-time PCR revealed increased VDR mRNA expression in live M. tuberculosis-stimulated culture in PTB patients (p < 0.01) than normal healthy subjects. Cathelicidin mRNA expression was significantly increased in vitamin D₃-treated cultures compared to unstimulated and M. tuberculosis-stimulated culture in both patients (p < 0.001) and NHS (p < 0.05). Conclusions  The present study suggests that PTB patients may have increased 1,25(OH)₂ D₃ levels, and this might lead to downregulation of VDR expression. Decreased VDR levels could result in defective VDR signaling. Moreover, addition of 1,25(OH)₂ D₃ might lead to increased expression of cathelicidin which could enhance the immunity against tuberculosis.     

Do Vitamin D receptor gene polymorphisms affect bone mass density in men?: A meta-analysis of observational studies

The signs of aging in humans can often be detected through a decrease in bone mass density (BMD). The decrease in BMD as a risk of osteoporosis is often only seen in women, but not in men, even though men also have a risk of osteoporosis which can affect their well-being. We conducted study searches through databases such as PubMed, EBSCO, ProQuest, Willey Online, Science Direct, and SAGE. We performed analysis on four types of Vitamin D receptor polymorphisms: BsmI, ApaI, FokI, and TaqI from 14 potential studies involving men. We found that several genetic analysis models of BsmI and FokI significantly affected BMD in men: BB vs bb in whole body BMD (SMD = 0.43, 95% CI = [0.12–0.75], p = 0.0008, BB vs Bb in whole body BMD (SMD = −1.38, 95% CI = [−1.87 to 0.88], p < 0.00001), and FF+Ff vs ff spine BMD (SMD = 0.59, 95% CI = 0.13–1.05], p = 0.001), even after adjusting for comorbidities as confounding variables. The present meta-analysis showed that BsmI and FokI polymorphisms of the VDR gene were correlated with decreased BMD in men which may contribute to the aging process and well-being.     

汉族人维生素D受体基因TruⅠ酶切位点多态性及其对BsmⅠ酶切位点多态性测定的影响

目的测定汉族人维生素D受体基因TruⅠ酶切位点多态性分布并探讨其对BsmⅠ酶切位点多态性分布测定的影响。方法收集80名健康汉族人外周静脉血标本,提取基因组DNA,用限制性片段多态性长度酶切法测定80名汉族人维生素D受体基因TruⅠ、BsmⅠ酶切位点多态性;换用常规引物再次测定上述标本BsmⅠ酶切位点多态性;分析维生素D受体基因TruⅠ、BsmⅠ酶切位点多态性及两次测定的BsmⅠ位点的一致性。结果测得TruⅠ基因型频率为TT68.7%,Tt26.3%,tt5.0%;同一PCR片段上测得BsmⅠ位点基因型频率为BB6.2%,Bb52.5%,bb41.3%,多态性分布均符合Hardy-Weinberg平衡;换用常规引物测定同批标本BsmⅠ位点多态性,基因型分布为BB20.0%,Bb26.2%,bb53.8%,不符合Hardy-Weinberg平衡（r=13.29,P〈0.01）。与第1次测定相比,有22个标本基因型由Bb型变成BB型或bb型,发生基因型丢失。结论汉族人VDR基因存在TruⅠ多态性,其多态性分布与其它种族不同;TruⅠ酶切位点多态性可引起BsmⅠ位点多态性测定时等位基因的丢失。     

Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case–control studies

Vitamin D receptor (VDR) polymorphisms have been studied as potential contributors to multiple sclerosis (MS). However, published studies differ with respect to study design and the significance of the effects detected. The aim of this study was to quantify the magnitude of the risk associated with the TaqI, BsmI, ApaI and FokI VDR polymorphisms in MS using a meta-analysis approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search and meta-analysis of the literature. Subgroup analyses were performed to detect potential sources of heterogeneity from the selected study characteristics. The stability of the summary risk was evaluated using sensitivity analyses. The meta-analysis included a total of 3300 cases and 3194 controls from 13 case–control studies. There were no significant associations found between TaqI and BsmI polymorphisms and MS risk. The association between the ApaI polymorphism and MS risk was significant in the homozygous and codominant models (P=0.013 and P=0.031, respectively), suggesting that the AA ApaI genotype might be a significant MS risk factor. Publication year and age significantly affected the association between TaqI polymorphisms and MS (P=0.014 and P=0.010, respectively), which indicates a protective effect of the major T allele. The AA ApaI and FF FokI genotypes are significant risk factors for MS. The association between the TaqI polymorphism and MS risk is significantly affected by study characteristics.     

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.     

维生素D受体基因起始密码和3‘端多态性与绝经后妇女骨密度的关系

目的：了解维生系D受体（vitamin d receptor,VDR)基因起始密码多态性和3'端多态性对北京地区汉族绝经后妇女骨密度（bone mineral density,BMD)值的影响是否具有协同作用。方法：应用聚合酶链反应－限制性片段长度多态性检测了110绝经后妇女VDR基因Fok 1和3'端多态性，同时用双能X线吸收法测定绝经后妇女腰椎2－4（L2－4）、股骨颈、Ward's三角和大转子区的BMD值。结果：被研究人群Fok I、Apa I、Bsm I和Taq I等位频率分布均符合Hardy-Weinberg定律。单独分析各基因型与绝经后妇女BMD值的关系，仅显示Bsm I基因型与BMD值有关联（P＜0．05）；协同分析Fok I基因型和Apa I、Bsm I、Taq I基因型与BMD值的关系，显示Fok I-Apa I基因型与绝经后妇女L2－4 BMD值显著相关（P＜0．001），而未见Fok I-Bsm I基因型与绝经后妇女各部位BMD值的关联，Fok I-Taq I基因型与股骨颈和大转子区部位BMD值有关联（P＜0．05）。此外，未发现VDR基因3'端多态性之间与各部位的BMD值有关联。结论：VDR基因Fok I多态性虽然与绝经后妇女BMD值无关联，但Fok I多态性和3'端多态性（Apa I和Taq I）对绝经后妇女BMD值的影响具有协同作用。     

5′ Regulatory and 3′ Untranslated Region Polymorphisms of Vitamin D Receptor Gene in South Indian HIV and HIV–TB Patients

Introduction  Vitamin D receptor (VDR) gene polymorphisms in the 5′ regulatory region (Cdx2 and A-1012G), coding region (FokI), and 3′ untranslated region (UTR; BsmI, ApaI, and TaqI) were studied to find out whether these polymorphisms are associated with susceptibility to or protection against HIV-1 and development of tuberculosis (TB) in human immunodeficiency virus (HIV)-1-infected patients. Study Subjects and Methods  The study was carried out in 131 HIV patients without TB (HIV+ TB−) and 113 HIV patients with TB (HIV+ TB+; includes 82 patients with pulmonary TB (HIV+ PTB+) and 31 with extra pulmonary TB), 108 HIV-negative pulmonary TB patients (HIV− PTB+), and 146 healthy controls. Results  Among the 5′ regulatory and coding region polymorphisms, significantly increased frequency of G/A genotype of Cdx-2 was observed in HIV+ TB− group compared to controls (p = 0.012, odds ratio (OR) 1.89 95% confidence interval (CI) 1.14–3.15). In the 3′ UTR genotypes, a decreased frequency of b/b genotype of BsmI in total HIV patients (p = 0.014, OR 0.54 95% CI 0.32–0.89) and increased frequencies of A/A genotype of ApaI in HIV+ TB+ patients (p = 0.041, OR 1.77 95% CI 1.02–3.06) and t/t genotype of TaqI in HIV+ PTB+ patients (p = 0.05, OR 2.32 95% CI 0.99–5.46) were observed compared to controls. Haplotype analysis revealed significantly increased frequencies of 3′ UTR haplotype B-A-t in HIV+ TB+ and HIV+ PTB+ groups (Pc = 0.030, OR 1.75 95% CI 1.14–2.66) and decreased frequencies of b-A-T haplotype in total HIV patients (Pc = 0.012, OR 0.46 95% CI 0.27–0.77), HIV+ TB− (p = 0.031 OR 0.48 95% CI 0.25–0.89), and HIV+ PTB+ groups (Pc = 0.04, OR 0.47 95% CI 0.23–0.89) compared to controls. Conclusions  The results suggest that VDR gene 3′ UTR haplotype b-A-T may be associated with protection against HIV infection while B-A-t haplotype might be associated with susceptibility to development of TB in HIV-1-infected patients.     

Regulatory role of Cdx-2 and Taq I polymorphism of vitamin D receptor gene on chemokine expression in pulmonary tuberculosis

Vitamin D receptor (VDR) gene variants have been shown to be regulating the immune response in tuberculosis. We studied the regulatory role of VDR promoter Cdx-2 and 3′UTR TaqI gene variants on chemokine levels from culture filtrate antigen (CFA) stimulated with or without 1,25(OH)₂D₃ treated peripheral blood mononuclear cells of 50 pulmonary tuberculosis patients (PTB) and 51 normal healthy controls (HCs). In CFA with 1,25(OH)₂D₃ treated cultures, the MIP-1α, MIP-1β, RANTES levels were significantly decreased in Cdx-2 AA genotype compared to GG genotype, while a significantly increased MIG level was observed in Cdx-2 AA genotype (p < 0.05). In TaqI polymorphism, tt genotype significantly decreased MIP-1β and RANTES levels compared to TT genotype. Moreover, a significantly increased level of IP-10 and MIG was observed in TaqI tt genotype compared with TT genotype (p < 0.05). The results suggests that the 1,25(OH)₂D₃ may alter the chemokine response through the VDR polymorphic variants during infection.     

Association of vitamin D receptor and estrogen receptor gene polymorphisms with bone mass in postmenopausal Korean women

OBJECTIVE: To examine the relationship between vitamin D receptor (VDR) and estrogen receptor (ER) gene polymorphism and bone mineral density (BMD). DESIGN: Polymorphisms at the VDR FokI and ER PvuII and XbaI gene sites, serum bone-specific alkaline phosphatase, urinary N-telopeptide of type I collagen, and BMD at the lumbar spine and proximal femur were analyzed in 229 postmenopausal Korean women. RESULTS: The distribution of ER PvuII and XbaI and VDR FokI restriction fragment length polymorphisms was as follows: pp 39.3%, Pp 46.3%, PP 14.4%, xx 34.1%, Xx 61.1%, XX 4.8%. ff 17.0%, Ff 43.7%, and FF 39.3%, respectively (upper-case letters signify the absence, and lower-case letters signify the presence of the restriction site). After adjusting for potential confounding factors such as age, body mass index, and menopause duration, ER PvuII was independently associated with BMD at the lumbar spine and XbaI polymorphism BMD at the femoral neck. The lumbar spine BMD in the pp genotype was 7.5% lower than in the PP genotype, and the femoral neck BMD was 4.8% lower in the Xx genotype than in the xx genotype. By itself, the VDR FokI polymorphism was not related to BMD, but by combining the FokI genotype (FF) with ER genotypes, such as ppxx and the PpXx, the difference in the BMD at the Ward's triangle became significant. There were no significant differences in the levels of biochemical markers between the genotypes of three polymorphisms. CONCLUSION: ER polymorphisms, singly and in relation to VDR FokI polymorphism, influence bone mass in Korean women.     

Staphylococcus aureus nasal carriage might be associated with vitamin D receptor polymorphisms in type 2 diabetes

Vitamin D receptor (VDR) gene polymorphisms have been associated with susceptibility to several diseases, including type 1 diabetes (T1D), type 2 diabetes (T2D), and various infections. The study investigated whether VDR gene polymorphisms influence nasal carriage of Staphylococcus aureus in individuals with T2D, an important source for bloodstream, surgical site and other nosocomial infections. In 173 patients with T2D genotyped for the VDR gene polymorphisms on FokI (rs10735810) F>f, BsmI (rs1544410) B>b, ApaI (rs7975232) A>a, and TaqI (rs731236) T>t, a nasal swab was obtained to detect colonization by S. aureus. A repeat swab was obtained in 162/173 subjects for the estimation of persistent S. aureus carriage. The prevalence of S. aureus nasal colonization was 19.7% and of persistent carriage was 8.6%. Nasal colonization by S. aureus was more common in individuals with FokI f allele than F allele (p 0.05; OR 1.69, 95% CI 1.00–2.89) and individuals with FokI ff genotypes were more frequently colonized than those with FokI FF and Ff genotypes combined (p 0.03; OR 2.61, 95% CI 1.14–5.99). The presence of the FokI f allele was related to higher rates of S. aureus persistent nasal colonization (p 0.002; OR 3.53, 95% CI 1.56–7.98), and individuals with a FokI ff genotype were more often persistent carriers than those with FokI FF and Ff genotypes combined (p <0.001; OR 7.32, 95% CI 2.39–22.41). This study is the first, to our knowledge, to show an association between FokI polymorphism in the VDR gene and nasal carriage of S. aureus in individuals with T2D.     

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.     

广州地区绝经后妇女维生素D受体基因多态性与骨密度关系的研究

目的：了解广州地区绝经后妇女维生素D受体基因多态性的分布，并进一步研究其与骨密度的关系。 方法：应用聚合酶链反应-限制性片段长度多态性（PCR-RFCP）等生物学技术检测203例绝经后广州地区妇女维生素D受体(VDR)基因型，同时用双能X线骨密度测量仪检测腰椎、股骨颈、瓦氏三角、大转子处骨密度（BMD）。 结果：203例受试对象中，VDR基因型分别为BB型17例（占8.3%）、Bb型60例（占29.6%），bb型126例（占62.1%）， b等位基因频率为76.85%、B等位基因频率为23.05%，基因型分布符合Hardy-Weinberg定律。分析其基因型与骨密度的关系显示：只有bb与Bb、BB基因型在腰椎骨密度存在差异（P<0.05）、Bb与BB的腰椎BMD无差异（P>0.05），其余部位3种基因型骨密度无差异（P>0.05）。 结论： VDR基因型与BMD间存在着一定关联，但尚不能作为预测广州绝经后妇女发生骨质疏松危险性的遗传标志。     

Vitamin D receptor gene polymorphism and susceptibility to asthma: Meta-analysis based on 17 case-control studies

BackgroundDuring the last decade, several studies have evaluated the potential association between vitamin D receptor (VDR) gene polymorphism and susceptibility to asthma. In spite of valuable findings, the results are still contradictory. Therefore, a comprehensive meta-analysis not only solves discrepancies but provides a clue for future projects.ObjectiveThis meta-analysis was performed to identify whether VDR gene polymorphisms (FokI (rs2228570) or TaqI (rs731236) or BsmI (rs1544410) or ApaI (rs7975232)) play a role in the risk of asthma.MethodsElectronic search of Web of Science, Scopus, and PubMed databases were systematically conducted from their inception until June 2019, to identify all published studies. Eligibility of the studies was confirmed by precise inclusion and exclusion criteria, and the resultant studies were analyzed.ResultsA total of 17 studies concerning VDR gene polymorphisms and asthma risk were included in this meta-analysis. The results of pooled analysis indicated a statistically significant association between FokI SNP (dominant model [OR = 0.78, 95% CI, 0.62-0.98, random effect model] and allelic model [OR = 0.81, 95% CI, 0.67-0.98, random effect model]) and TaqI SNP (homozygote contract model [OR = 0.70, 95% CI, 0.54-0.89]) with asthma risk. Moreover, subgroup analysis showed that ethnicity influences asthma risk in Asian, African, and American populations. The sensitivity analyses confirmed the stability of the results.ConclusionThis meta-analysis suggests that VDR gene polymorphism is associated with the risk of asthma.