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.     

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.     

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.     

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.     

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.     

Association of vitamin D receptor polymorphisms with the outcome of allogeneic haematopoietic stem cell transplantation

Recently, vitamin D receptor (VDR) polymorphism has been identified as an additional genetic factor associated with the outcome after allogeneic haematopoietic stem cell transplantation (HSCT) from HLA-matched sibling donors. In the present study, VDR ApaI, TaqI and FokI alleles were typed using single strand conformation polymorphism in 123 Polish recipients and their sibling or alternative donors to test the associations of VDR polymorphisms with HSCT outcome. Four VDR genotypes were identified as risk factors of acute graft-versus-host disease (aGVHD). Donor ApaI AA (OR = 7.245, P = 0.009), source of HSC (OR = 7.001, P = 0.007), transplantation from an alternative donor (OR = 6.630, P = 0.007) and donor FokI FF (OR = 4.473, P = 0.025) significantly contributed to the development of grades II-IV aGVHD, while recipient ApaI aa (OR = 3.233, P = 0.069), recipient FokI FF (OR = 2.558, P = 0.077) and female to male transplants (OR = 2.955, P = 0.099) were found to be less significant factors. In addition, the presence of ApaI aa genotype in the recipient was found to be associated with increased likelihood of death (P = 0.0228). The present study contributes to the studies demonstrating a role of VDR polymorphisms in HSCT outcome. In addition to previously described correlations of ApaI a allele and occurrence of severe grades III-IV aGVHD and (linked with ApaI aa) recipient TaqI TT genotype with aGVHD, the novel associations of recipient and donor FokI FF genotype and the increased aGVHD risk and recipient ApaI aa with survival were identified.     

Association of HLA-DR, -DQ, and vitamin D receptor alleles and haplotypes with tuberculosis in the Venda of South Africa

The vitamin D receptor (VDR) and the human leukocyte antigen (HLA) class II complex affect innate and/or adaptive immunity against Mycobacterium tuberculosis. HLA-DRB1, HLA-DQB1, and VDR gene (VDR) polymorphisms were previously associated with tuberculosis (TB) and are here investigated as candidates for TB susceptibility in the Venda population of South Africa. Genomic DNA from 95 patients with pulmonary tuberculosis (PTB) and 117 ethnically matched, healthy controls were typed for HLA-DRB1, DRB3, DRB4, DRB5, DQB1, and VDR polymorphisms FokI, BsmI, ApaI, and TaqI using polymerase chain reaction-sequence specific primers (PCR-SSP). Allele and haplotype frequencies were calculated by the estimator maximum (EM) algorithm. DRB1*1302 phenotype was significantly associated with TB occurring at a significantly higher allele frequency in cases than controls and found in haplotype with DQB1*0602/3. DQB1*0301-0304 phenotype was significantly associated with TB and found in haplotype with DRB1*1101-1121, showing significant linkage disequilibrium (LD) in both cases and controls. Only DRB1*1101-1121-DQB1*05 was significantly associated with TB based on the sequential Bonferroni p value. VDR SNP phenotypes were not associated with TB, but the haplotype F-b-A-T significantly protected from TB. In conclusion, common African HLA-DRB1 and -DQB1 variants, previously associated with protection from malaria and hepatitis B/C virus persistence, predispose the Venda to TB, whereas the proposedly active VDR haplotype F-b-A-T showed significant protection.     

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.     

Association of vitamin D receptor gene polymorphisms with bone mineral density in postmenopausal women of Hellenic origin

OBJECTIVES: There are numerous indications that genetic factors play an important role in the pathogenesis of osteoporosis, a common condition characterized by reduced bone mass and increased fracture risk. The vitamin D receptor (VDR) gene has been suggested as a possible candidate gene for the regulation of bone mass but the relationship between VDR polymorphisms and bone mineral density (BMD) is controversial and has not been confirmed by all workers in different ethnic groups studied. METHODS: In order to evaluate the contribution of the VDR alleles in bone mass loss, the BsmI, ApaI and TaqI polymorphisms in the VDR gene were studied in 126 postmenopausal women. RESULTS: It was found that the bb, aa and TT genotypes and the bAT and baT haplotypes were associated with a lower BMD measured at the forearm. CONCLUSIONS: Our analysis reveals a significant association between VDR gene alleles and bone mass in the population studied.     

Association of estrogen and vitamin D receptor gene polymorphisms with tooth loss and oral bone loss in Japanese postmenopausal women

OBJECTIVE: To investigate the relationship between estrogen receptor (ER) and vitamin D receptor (VDR) gene polymorphisms and tooth loss, oral bone loss, and postcranial bone mineral density (BMD) in Japanese postmenopausal women. DESIGN: Polymorphisms at the ER PvuII and XbaI and VDR BsmI gene sites, number of teeth remaining, oral bone mass, and BMD of the lumbar spine and the hip were evaluated in 149 Japanese postmenopausal women. RESULTS: The distribution of ER PvuII and XbaI and VDR BsmI restriction fragment length polymorphisms was as follows: pp, 30.2%; Pp, 49.7%; PP, 20.1%; xx, 71.8%; Xx, 22.5%; XX, 2.7%; bb, 76.5%; Bb, 22.2%; and BB, 1.3%. Analysis of covariance adjusted for confounding variables revealed that participants with pp allele had fewer teeth remaining than did those with P allele. There were no significant differences in oral bone mass and postcranial BMD among three alleles at the PvuII site. Participants with X and bb allele had less oral bone mass and lower postcranial BMD than did those with xx and B allele, respectively. We could not clarify the positive associations between XbaI and BsmI polymorphism and number of teeth. CONCLUSIONS: PvuII polymorphism was associated with tooth loss, but not with oral bone mass and postcranial BMD. XbaI and BsmI polymorphisms may be associated with bone mass or density; however, PvuII polymorphism might contribute to another unknown pathway related to tooth loss.     

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.     

Analysis of vitamin D receptor gene polymorphisms in women with and without endometriosis

An aberrant immunologic mechanism has been suggested to be involved in the pathogenesis of endometriosis. Genetic alterations in the vitamin D receptor gene (VDR) may lead to important defects in gene activation that principally affect immune function. We have hypothesized a possible relationship between endometriosis and/or infertility and the VDR polymorphisms (ApaI, TaqI, FokI, and BmsI). The study was a case-control study including 132 women with endometriosis-related infertility, 62 women with idiopathic infertility, and 133 controls. VDR polymorphisms were studied by restriction fragment length polymorphism. We found relatively similar VDR polymorphism genotype frequencies in cases and controls. When patients with minimal/mild and moderate/severe endometriosis were studied separately, no difference was found. When we compared infertile groups with and without endometriosis there was no statistically significant difference. The data suggest that VDR polymorphisms did not play an important role in the pathogenesis of endometriosis and/or infertility in the Brazilian women studied.     

Polymorphisms at the ligand binding site of the vitamin D receptor gene and osteomalacia

Vitamin D receptor (VDR) gene polymorphisms have been suggested as possible determinants of bone mineral density (BMD) and calcium metabolism. In this study, our aim was to determine whether there is an association between VDR gene polymorphism and osteomalacia or not. We determined ApaI and TaqI polymorphisms in the vitamin D receptor gene in 24 patients with osteomalacia and 25 age-matched healthy controls. Serum calcium, phosphorus, ALP, PTH, 25OHD levels were also examined. We used PCR and RFLP methods to test for an association between osteomalacia and polymorphisms within, intron 8 and exon 9 of the VDR gene. When the control and patients were compared for their ApaI and TaqI genotypes there was no relationship between VDR gene allelic polymorphisms and osteomalacia. Whereas a nearly significant difference for A allele was found in the allellic distribution of the patients (p=0.08). Also no association between biochemical data and VDR gene polymorphisms was observed.     

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.     

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.     

Vitamin D receptor ApaI (rs7975232), BsmI (rs1544410), Fok1 (rs2228570), and TaqI (rs731236) gene polymorphisms and susceptibility to pulmonary tuberculosis in an Iranian population: A systematic review and meta-analysis

Polymorphisms of vitamin D receptors (VDRs), ApaI, BsmI, FokI, and TaqI might affect susceptibility to tuberculosis (TB). In this systematic review and meta-analysis, all published articles which investigated the effects of these polymorphisms on the risk of TB in the Iranian population were retrieved.PubMed and Scopus were searched with no date or language restrictions. In this meta-analysis, the Comprehensive Meta-Analysis (CMA) version 2.0 and random effects model were applied. The association of polymorphisms with TB risk was assessed by measuring the odds ratio (ORs) at 95% CI. Heterogeneity was investigated based on Cochran Q-test and I2-index statistics. The significance level was set at 0.05. Also, Egger's regression intercept was determined to measure publication bias.A total of six articles on Iranian populations were included. TaqI (5/6 included studies) showed a significant association with the increased risk of TB based on ORs (allele comparison: 1.57 (1.0, 2.3), p-value: 0.02; additive model of tt/TT: 1.57 (0.9, 2.5), p-value: 0.05; recessive model (tt/Tt + TT): 1.99 (1.2, 3.2), p-value: 0.00; dominant model (tt + Tt/TT): 1.98 (1.1, 3.5), p-value: 0.01). BsmI showed a significant positive effect on TB risk only in its dominant genotype (bb + bB/BB) (1.44 (1.0, 1.9); p-value: 0.02). FokI and ApaI did not show any significant effects on TB development in Iranian populations. Findings showed the significant effect of TaqI polymorphism in all genetic models and the dominant model of BsmI on the increased risk of TB. However, the effects of TaqI and BsmI should be further investigated in a larger sample size.     

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.     

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.     

Serum Vitamin D Levels and VDR Polymorphisms (BsmI and FokI) in Patients and their Household Contacts Susceptible to Tuberculosis

Vitamin D, an immunomodulator of macrophage function, can activate human antimycobacterial activity. Vitamin D deficiency (VDD) is associated with an impaired mycobacterial immunity and susceptibility to tuberculosis. It has been found that vitamin D and its receptor may be essential for immune function. In this study, we examined the serum 25(OH) vitamin D levels and its receptor (VDR) polymorphisms with susceptibility to tuberculosis in patients, household contacts and healthy controls. Serum 25(OH) vitamin D levels were measured in 75 cases (25 patients, 25 household contacts and 25 healthy controls), and polymorphisms (BsmI and FokI) were carried out in 335 cases (110 patients, 110 household contacts and 115 healthy controls). The proportion of serum 25(OH) vitamin D deficiency and insufficiency was high in patients (44, 58%) and household contacts (40, 48%) compared to controls (48%). The BB and Bb genotypes of BsmI were significantly associated in patients (P < 0.014; OR: 0.509; CI: 0.265–0.876) (P < 0.001; OR: 2.351; CI: 1.368–4.041) and household contacts (P < 0.04; OR: 0.575; CI: 0.336–0.985); (P < 0.002; OR: ?2.267; CI: 1.32–3.895) when compared to healthy controls. The diplotype and MDR analysis showed the high‐risk genotypes of BsmI and FokI polymorphisms. Vitamin D deficiency and its association with VDR gene polymorphisms may be useful to identify the high‐risk group individuals.     

维生素D受体基因多态性与乙型肝炎病毒感染的关联研究

目的探讨中国汉族人群维生素D受体（vitamin D receptor，VDR）基因多态性是否与乙型肝炎病毒（hepatitis B virus，HBV）感染结局相关联。方法以184例慢性乙肝患者和205名无症状HBV携带者为研究对象，收集外周血，提取基因组DNA，应用聚合酶链反应．限制性片段长度多态性（polymerase chain reaction-restriction fragmentlength polymorphism，PCIR-RFLP）方法，分析VDR基因第2外显子Fok Ⅰ位点、第9外显子Taq Ⅰ位点的多态性分布。结果单因素分析结果显示Fok Ⅰ位点FF基因型在慢性乙肝组的频率44．6％显著高于无症状HBV携带组的31．7％（P〈0．05）。经多因素非条件Logistic回归分析调整混杂作用后，结果仍然显示FF基因型在慢性乙肝组与无症状HBV携带组之间的差异存在统计学意义（OR=1．95，P〈0．05）。FokⅠ位点与TapⅠ位点组成的FT单倍型在慢性乙肝组的分布频率显著高于无症状HBV携带组（OR=1．45，P〈0．05），fT单倍型在慢性乙肝组的分布频率显著低于无症状HBV携带组（OR=0．72，P〈0．05）。结论维生素D受体基因多态性可能影响HBV感染的遗传易感性。