维生素D受体基因ApaⅠ多态性与终末期肝病患者骨代谢的相关性研究

目的探讨维生素D受体（VDR）基因Apal位点多态性与终末期肝病患者骨代谢的关系。方法选择72例终末期肝病患者,并以50例原发性骨质疏松和骨量减少患者作为对照组。采用聚合酶链反应和限制性片段长度多态性技术（PCR-RFLP）检测VDR基因ApaⅠ位点多态性,双能X线吸收仪（DXA）检测腰椎（L1～4）及股骨颈骨密度（BMD）,并检测骨代谢相关指标,包括甲状旁腺激素（PTH）、骨钙素（BGP）、血钙（Ca）、血磷（P）、尿钙（uCa）、尿肌酐（uCr）。结果①Apa Ⅰ多态性等位基因频率分布符合Hardy—Weinberg定律,终末期肝病组基因型分布为AA（12．5％）、Aa（34．7％）、aa（52．8％）;对照组基因型分布为AA（10．0％）、Aa（36．0％）、aa（54．0％）。基因型分布频率两组间差异无统计学意义（P〉0．05）。②终末期肝病组中,ApaⅠ基因型与L1～4及股骨颈BMD相关（P〈0．01）,AA基因型L1-4及股骨颈的BMD显著高于aa型（P〈0．05）。对照组中,ApaⅠ基因型与L1-4及股骨颈BMD均无明显相关性。③终末期肝病组中,ApaⅠ基因型与BGP水平相关,AA基因型的BGP水平高于aa型（P〈0．05）;ApaⅠ基因型与PTH、血Ca、血P及uCa／Cr水平差异无统计学意义。结论终末期肝病患者VDR基因ApaⅠ位点多态性与BMD及BGP水平均相关,ApaⅠ位点多态性与终末期肝病患者骨代谢存在相关性。     

降钙素受体基因多态性与特发性高钙尿症的相关性研究

目的了解降钙素受体（CTR）基因单核苷酸多态性与特发性高钙尿症的关系，探讨特发性高钙尿的发病机理。方法提取湖北地区76例汉族特发性高钙尿患者及126例健康对照者外周血标本基因组DNA，应用聚合酶链反应-限制性片段长度多态性方法检测并分析CTR基因核苷酸序列1377位点C／T单核苷酸多态性分布。结果2组标本CTR基因C／T多态性位点等位基因频率分布均符合Hardy-Weinberg定律，患者组CC、TC、TT基因型分布频率分别为73．7％、17．1％、9．2％，对照组分别为89．7％、9．5％、0．8％；2组等位基因c、T分布频率分别为84．2％、15．8％和94．4％、5．6％，患者组等位基因T和TT基因型分布频率高于对照组，而等位基因C和CC基因型的分布频率低于对照组，差异有统计学意义（P〈0．05）。结论CTR基因1377多态性位点C／T单核苷酸多态性在湖北地区汉族人群特发性高钙尿的发生中起重要作用。     

福建地区汉族人群VDR基因TaqⅠ多态性与腰椎间盘退行性变的相关性研究

目的研究维生素D受体（VDR）基因TaqⅠ多态性与福建地区汉族人群腰椎间盘退行性变的关系。方法应用限制性片段长度多态性聚合酶链反应法（PCR-RFLP）对78例腰椎椎间盘退行性疾病（DDD）（腰椎DDD组）及79例非腰椎DDD的健康体检者（对照组）的外周血进行VDR基因TaqⅠ多态性检测,分析2组间基因型和等位基因的频率分布;研究其中小于45岁者基因型及基因频率分布与椎间盘退变程度的关系。结果腰椎DDD组基因型分布：TT 96.2%（75/78）,Tt 3.8%（3/78）;对照组TT 81.0%（64/79）,Tt 19.0%（15/79）。其中TT基因型分布在2组中的差异有统计学意义（P〈0.05）。腰椎DDD组与对照组等位基因T分布频率分别为98.1%（153/156）和90.5%（143/158）,t分别为1.9%（3/156）和9.5%（15/158）,差异有统计学意义（P〈0.05）;在MRI分组中VDR基因TaqⅠ酶切位点的基因型和等位基因频率在组中分布差异有统计学意义（P〈0.05）。结论 VDR基因TaqⅠ多态性与福建地区汉族人群腰椎间盘退行性变发生有一定关系。     

钙敏感受体基因第7外显子单核苷酸多态性与特发性高钙尿症的关系

目的了解钙敏感受体（CaSR）基因单核苷酸多态性与特发性高钙尿（IH）症的关系，探讨特发性高钙尿发病的分子机制。方法提取76例湖北地区汉族特发性高钙尿患者及126例健康对照者外周血标本中基因组DNA，应用聚合酶链反应（PER）结合DNA测序方法检测并分析了CaSR基因的第7外显子3个簇集的多态性位点单核苷酸多态性分布。结果特发性高钙尿病例和对照组CaSR基因的第7外显子第986、990多态性位点等位基因频率分布均符合Hardy-Wein-berg定律，其基因型分布频率在特发性高钙尿患者和正常对照者中差异无统计学意义（P〉0．05），第1011位未见有多态改变。但特发性高钙尿组组内CaSR 990位GG纯合子和RG杂合子个体的24h尿钙排泄量较RR纯合子明显增高，差异有统计学意义（P〈0．05）。结论CaSR基因不是特发性高钙尿的易感主基因，但第7外显子990位A／G单核苷酸多态性能影响尿钙排泄，可能是特发性高钙尿中调节钙排泄的遗传成分之一。     

维生素D受体基因Apal多态性与核心家庭女性峰值骨密度关系研究

目的 探讨维生素D受体（VDR）基因ApaⅠ多态性与中国核心家庭女性峰值骨密度（BMD）的关系。方法 收集上海市401个由汉族父母双亲和至少一个健康女儿（年龄在20～40岁）组成的核心家庭。运用双能X线吸收仪测量女儿腰椎1～4和股骨颈、大转子、粗隆间、总髋部及Ward’s三角的BMD值（g／cm^2）。PCR-RFLP方法分析所有研究对象VDR基因ApaⅠ多态性。用协方差分析（ANCOVA）和数量性状位点传递非平衡测验法（QTDT）对ApaⅠ多态性与BMD进行相关、连锁和相关模型下的连锁分析。结果 基因型频率分布符合Hardy-weinberg平衡定律。ANCOVA显示VDR基因ApaⅠ多态性与女性腰椎峰值BMD相关（P=0．047）；QTDT分析未发现VDR基因ApaⅠ多态性与腰椎及股骨近端各部位BMD值的相关和连锁。结论 本研究提示VDR基因ApaⅠ多态性与上海市女性峰值BMD值变异无关联和连锁。VDR基因ApaⅠ多态性不是上海市汉族女性峰值BMD值变异的数量性状位点。     

维生素D受体基因Apa I多态性与骨质疏松症相关性的研究

目的研究维生素D受体（vitamin Dreceptor,VDR）基因ApaⅠ多态性与原发性骨质疏松症的相关性。方法应用聚合酶链反应-限制性片段长度多态性分析技术测定山东半岛地区155例骨质疏松患者和113例对照者维生素D受体基因ApaⅠ多态性,比较两组基因型和等位基因分布频率。结果两组基因型和等位基因差异有显著性（P〈0.05）。男性及〈65岁骨质疏松组同相应对照组相比差异无显著性,女性及≥65岁骨质疏松组同相应对照组相比差异有显著性（P〈0.05）;≥65岁女性骨质疏松组aa基因型与a等位基因频率高于其对照组。结论山东半岛地区汉族人群中,维生素D受体基因ApaⅠ多态性与原发性骨质疏松症存在相关性,65岁及以上女性a等位基因是易感基因,aa基因型个体存在易感性。     

维生素D受体基因Taq Ⅰ位点多态性与亚洲男性前列腺癌易感性的Meta分析

目的探讨维生素D受体（VDR）基因Taq Ⅰ位点多态性与亚洲男性前列腺癌易感性的关系。方法检索PubMed、中国知网、万方数据库、维普中文科技期刊,获取VDR基因Taq I位点多态性与亚洲男性前列腺癌易感性的病例-对照研究。以前列腺癌组与对照组人群基因型分布的OR值为效应指标,采用固定或随机效应模型进行合并分析,并进行偏倚评估,应用STATA10.0软件进行统计学处理。结果共纳入文献10篇,研究10项,累计前列腺癌病例1 141例,对照1 685例。与等位基因T相比,C等位基因合并的OR（95%CI）为0.81（0.70~0.94）;与野生基因型TT相比,CT和CC＋CT基因型合并的OR（95%CI）分别为0.86（0.74~1.01）和0.84（0.73~0.97）。结论 VDR基因Taq Ⅰ位点变异可能会降低亚洲男性个体患前列腺癌的危险性。     

载脂蛋白AⅠ-CⅢ-AⅣ基因簇Xmn Ⅰ、Msp Ⅰ位点多态性与胆固醇结石病关系的研究

目的探讨载脂蛋白（Apo）AⅠ—CⅢ-AⅣ基因簇多态性与胆囊胆固醇结石病的关系，揭示胆固醇结石病的遗传易感性。方法应用多聚酶链反应技术（PCR）对胆固醇结石病患者及正常对照者ApoAⅠ—CⅢ-AⅣ基因簇的限制性片段长度多态性进行研究，检测ApoAⅠ-CⅢ-AⅣ基因位点XmnAⅠ及MspAⅠ。结果胆石组和对照组均以X1、M1等位基因为主，多为X1X1、M1M1纯合子基因型。胆石组各基因型和各等位基因频率与对照组比较，差异无统计学意义（P〉0．05）。胆石组女性患者正常型基因X1X1纯合子频率和正常等位基因X1的频率低于对照组女性，突变型基因X1X2杂合子、X2X2纯合子以及突变型等位基因X2的频率均高于对照组女性，差异有统计学意义（P〈0．05）。胆石组男性患者正常型基因M1M1纯合子频率低于对照组男性，而突变型基因M1M2杂合子频率高于对照组男性，差异有统计学意义（P〈0．05）。结论ApoAⅠ—CⅢ-AⅣ基因簇XmnⅠ位点的多态性可能与女性胆囊胆固醇结石病有关，而MspⅠ位点的多态性可能与男性胆囊胆固醇结石病有关。     

中国北方人群维生素D受体基因多态性与腰椎退变性椎间盘疾病关联研究

背景：退变性椎间盘疾病（degenerative disc disease,DDD）的发生由机体内在基因和外在环境因素综合作用导致,维生素D受体（vitaminDreceptor,VDR）基因可能同腰椎DDD的发生存在相关性。 目的：探讨VDR基因多态性与腰椎DDD发生的关系。 方法：采用病例对照研究方法,以MRI确诊腰椎间盘退变患者118例为病例组,无腰椎间盘退变者112例为对照。应用VeraCode GoldenGate Genotyping Assay SNPs检测系统检测VDR基因的单核苷酸多态性（single nucleotide polymorphism,SNP）信息,分析两组VDR基因多态性的差异。 结果：筛查VDR基因16个位点,rs2239179等位基因在病例组和对照组中的分布频率存在差异（P=0．046）,经Permutation校正后差异无统计学意义（P=0．4299）,其他各位点等位基因在病例组和对照组中的分布频率差异均无统计学意义（P值均〉0．05）。VDR基因各位点基因型在病例组和对照组中的分布频率差异均无统计学意义（P值均〉0．05）。在非条件Logistic回归分析中,未发现VDR基因各位点符合Codominant、Dominant、Recessive、Overdominant或Log-additive遗传模型。在VDR基因的各单倍体型中,病例组和对照组间的频率分布差异均无统计学意义（P值均〉0．05）。 VDR基因多态性与腰椎DDD的发生可能无关。     

维生素D受体基因多态性对脊柱结核易感性的影响

目的：探讨维生素D受体（vitamin D receptor，VDR）基因多态性与中国湖南省汉族人群脊柱结核易感性的关系。方法：选取2004年10月至2006年2月我院收治的湖南省汉族新发脊柱结核患者42例（病例组）及志愿者64例（对照组），应用聚合酶链反应-限制性片断长度多态性分析技术检测两组对象VDR基因FokⅠ酶切位点多态性，并进行VDR基因分型。结果：VDR—FF、VDR—Ff与VDR—ff三种基因型在病例组和对照组中的分布频率分别为14．29％、35．71％、50％和23．45％、54．69％、21．86％；两组组间比较有显著性差异（P〈0．05）．其中VDR—ff基因型在病例组中的分布频率明显高于对照组，比值比（odds ratio，OR）为3．571（P〈0．05）．其95％可信区间（confidence interval，CI）为1．561～8.167。结论：VDR基因FokⅠ酶切值点多念性与湖南省汉族人群脊柱结核的易感性相关，VDR—ff基因型可能是其易感基因型。     

A systematic review of vitamin D receptor gene polymorphisms and prostate cancer risk

PURPOSE: Polymorphisms in the vitamin D receptor gene have been hypothesized to alter the risk of prostate cancer. However, studies investigating the associations between specific vitamin D receptor polymorphisms and prostate cancer risk have yielded inconsistent results. MATERIALS AND METHODS: We performed a meta-analysis of 26 studies evaluating the association between vitamin D receptor TaqI, poly(A), BsmI, ApaI, and/or FokI polymorphisms, and prostate cancer risk. RESULTS: The studies were heterogeneous in terms of study design, selection of cases and controls, and racial composition. Random effects models were used to estimate the pooled OR and 95% CI of each vitamin D receptor polymorphism under codominant, additive, dominant and recessive genetic models. Overall we did not find evidence to support an association between any of the vitamin D receptor polymorphisms and the risk of prostate cancer. For TaqI, which is the most studied vitamin D receptor polymorphism with 18 studies (total of 2,727 cases and 3,685 controls), the pooled OR was 1.00 (95% CI 0.85 to 1.18) for the Tt vs TT genotypes, 0.94 (95% CI 0.78 to 1.13) for the tt vs TT genotypes and 0.89 (95% CI 0.71 to 1.10) for the recessive model (tt vs Tt plus TT). ORs for the poly(A) microsatellite, BsmI, ApaI and FokI polymorphisms were similar. CONCLUSIONS: The results of this meta-analysis suggest that the vitamin D receptor TaqI, poly(A), BsmI, ApaI and FokI polymorphisms are not related to prostate cancer risk.     

Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans

Vitamin D has been shown to exert manifold immunomodulatory effects. Because type 1 diabetes is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse, we investigated the role of the vitamin D receptor (VDR) gene as a candidate for type 1 diabetes susceptibility. A total of 152 Caucasian families with at least one affected offspring were genotyped for four VDR restriction-site polymorphisms (FokI, BsmI, ApaI, and TaqI). Whereas the BsmI, ApaI, and TaqI polymorphisms are in strong linkage disequilibrium with each other, no significant linkage disequilibrium with the FokI site was observed. Extended transmission disequilibrium testing (ETDT) was used to detect preferential transmission of allelic combinations to affected offspring. We found significant haplotype-wise ETDT results for the BsmI/ApaI/TaqI (chi2 = 18.886, df = 7, P = 0.0086), the BsmI/TaqI (chi2 = 8.373, df = 3, P = 0.0389), and theApaI/TaqI (chi2 = 17.182, df = 3, P = 0.0006) haplotypes. The "At" and "Bt" alleles confer an increased risk, whereas "AT" and "at" are protective. The combination with the strongest susceptibility was the "BAt" haplotype (64% transmitted, P = 0.0106). Analysis of the FokI site does not provide more information on susceptibility (FokI/BsmI/ApaI/TaqI [chi2 = 24.702, df = 15, P = 0.0541]). These findings suggest a linkage of VDR itself or a nearby gene with type 1 diabetes susceptibility in Germans, confirming respective observations previously made in Indian Asians.     

Vitamin D receptor gene polymorphisms and the risk of fractures in older women. For the Study of Osteoporotic Fractures Research Group.

The association between vitamin D receptor gene polypmorphisms and bone mineral density is controversial. The relationship between vitamin D receptor genotype and risk of fracture is uncertain. To determine whether vitamin D receptor polymorphisms were associated with the risk of hip, vertebral, and other (nonhip, nonvertebral) fractures in elderly women, we conducted a case-cohort study within a prospective study of 9704 community-dwelling women aged 65 years and older. Vitamin D receptor allele and genotype frequencies in women who experienced first incident hip (n = 181), vertebral (n = 127), and other (n = 223) fractures were compared with those of control women selected randomly from the cohort. Average length of follow-up was 6.5, 3.7, and 5.4 years for women in hip, vertebral, and other fracture analyses, respectively. Vitamin D receptor polymorphisms were determined by polymerase chain reaction amplification of genomic DNA using TaqI and ApaI restriction site endonuclease digestion. All nonvertebral fractures were confirmed by X-ray reports; hip fractures were validated by review of X-ray films. Vertebral fractures were defined by morphometry using lateral spine radiography at baseline and an average of 3.7 years later. Allele or genotype frequencies did not differ between fracture cases and their respective controls. Vitamin D receptor genotype (defined by TaqI, ApaI, or the combination of TaqI and ApaI) was not significantly associated with the risk of hip, vertebral, or other fractures. For example, compared with the referent group of women with TT genotype, those with Tt and tt genotypes had similar age- and weight-adjusted risks of fracture at the hip (hazard ratios 0.9, 95% confidence interval [CI] 0.6-1.3, and 0.8, 95% CI 0.5-1.2, respectively), spine (odds ratios 1.1, 95% CI 0.7-1.8, and 0.7, 95% CI 0.4-1.3, respectively), or other skeletal site (hazard ratios 1.0, 95% CI 0. 7-1.4, and 1.0, 95% CI 0.7-1.5, respectively). These findings were not altered in additional analyses including those adjusted for and stratified by age, ethnic ancestry, calcaneal bone density, dietary calcium intake, use of calcium supplements, use of vitamin D supplements, and oral estrogen use. We conclude that Vitamin D receptor polymorphisms defined by TaqI and ApaI are not associated with the risk of fracture in older women. Our results suggest that determination of these vitamin D receptor polymorphisms is not a clinically useful test for the prediction of fracture risk in elderly women.     

Association of vitamin D receptor gene polymorphism with urolithiasis

PURPOSE: Recent studies suggest that allelic variations of the vitamin D receptor (VDR) gene can influence calcium absorption and excretion. Therefore, we studied the association of VDR gene polymorphism with urolithiasis. SUBJECTS AND METHODS: We studied 83 patients with urinary stones and 83 controls. Patients were scored for certain clinical characteristics, including long axis diameter of the largest stone (1 point-less than 10 mm. and 2-10 mm. or greater), number of stones (1 point-1 and 2-multiple) and history of calcium stone disease (1 point-absent and 2-present). They were classified into 3 groups according to the total score, including low-3, intermediate-4 or 5 and high-6 points. The 2 VDR gene polymorphisms TaqI and ApaI were detected by polymerase chain reaction-restriction fragment length polymorphism and their relationships with the urinary calcium level were examined. RESULTS: The incidence of TaqI Tt and tt genotypes was significantly higher in the high score group than in controls. The TaqI t allele was associated with a 5.2-fold increase in the risk of severe stone disease. The urinary calcium level in patients with the Tt and tt genotypes was also higher than in those with the TT genotype. The rate of the ApaI genotype was not different in the high score group and controls. CONCLUSIONS: The TaqI t allele of the VDR gene may be a risk factor for severe stone disease and recurrent stones.     

Vitamin D receptor gene polymorphisms are associated with increased risk and progression of renal cell carcinoma in a Japanese population

AIM: Biological and epidemiologic data suggest that 1 alpha, 25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) levels may influence development of renal cell carcinoma. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of 1,25(OH)(2)D(3) and additionally interacts with other cell signaling pathways that influence cancer progression. VDR gene polymorphisms may play an important role in risk of incidence for various malignant tumors. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of renal cell carcinoma (RCC) in a Japanese population. METHODS: To analyze risk of RCC depending on VDR polymorphism, a case-control association study was performed. The VDR gene polymorphisms at three locations, BsmI, ApaI and TaqI, were genotyped in 135 RCC patients and 150 controls in a Japanese population. Logistic regression models were used to assess the genetic effects on prognosis. RESULTS: Significant differences in the ApaI genotype were observed between RCC patients and controls (chi(2) = 6.90, P = 0.032). No statistical significant difference was found in the BsmI and TaqI polymorphisms. The frequency of the AA genotype in the ApaI polymorphism was significantly higher in the RCC patients than in the controls (odds ratio, 2.59; 95% confidence intervals, 1.21-5.55; P = 0.012). Multivariate regression analysis showed that the AA genotype was an independent prognostic factor for cause-specific survival (relative risk 3.3; P = 0.038). CONCLUSION: The AA genotype at the ApaI site of the VDR gene may be a risk of incidence and poor prognosis factor for RCC in the Japanese population. Additional studies with a large sample size and investigation of the functional significance of the ApaI polymorphism in RCC cells are warranted.     

Iron indices and vitamin D receptor polymorphisms in hemodialysis patients

Cardiovascular disease caused by accelerated atherosclerosis is the major determinant of morbidity and mortality in chronic kidney disease patients. Vitamin D and its analogs provide survival benefit for hemodialysis (HD) patients. Vitamin D exerts its effects through the vitamin D receptor (VDR) that is coded for by a gene showing several polymorphisms that, in turn, are associated with a variety of diseases and differential responses to vitamin D. In this study, we evaluated the association between 4 VDR polymorphisms (ie, those identified by the restriction enzymes BsmI, ApaI, TaqI, and FokI) and iron indices (serum iron, transferrin, transferrin saturation, and ferritin) in 88 hemodialysis patients routinely treated with vitamin D. The absence or presence of the BsmI, ApaI, TaqI, and FokI restriction sites were denominated B and b, A and a, T and t, F and f, respectively. Our results show that in HD patients with transferrin saturation <20%, the F allele was more frequent than in HD patients with transferrin saturation >20% (P = .03). This relationship may provide a link between VDR alleles and iron and nutritional markers, which are highly predictive variables of cardiovascular morbidity and mortality in hemodialysis patients.     

Associations between vitamin D receptor gene polymorphisms and ankylosing spondylitis in Chinese Han population: a case–control study

Summary

We assessed whether the vitamin D receptor gene polymorphisms (FokI, BsmI, ApaI, and TaqI) were associated with ankylosing spondylitis (AS) in a Chinese Han population. The TaqI polymorphism G allele was a risk factor in AS susceptibility.

Introduction

Previous studies have found that serum vitamin D levels are declined in patients with AS. The present study aims to evaluate the role of vitamin D receptor (VDR) gene polymorphisms in AS susceptibility in a Chinese Han population.

Methods

Four single nucleotide polymorphisms (SNPs) in the VDR gene (FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236)) were genotyped by the improved multiplex ligase detection reaction (iMLDR) method in 620 AS patients and 620 geographically and ethnically matched healthy controls. Haplotypes were constructed after linkage disequilibrium (LD) analysis.

Results

Statistically significant difference was only found in the TaqI polymorphism between AS patients and controls. The TaqI polymorphism G allele was higher in AS group than that in controls (OR [95 % CI]?=?1.624 [1.122–2.352], χ ²?=?6.705, P?=?0.006). Linkage disequilibrium has been detected in TaqI and BsmI polymorphisms (D′?=?0.87, r ²?=?0.70). Two novel haplotypes (H1: AC and H2: GT) were significantly associated with the risk of AS, and they play protective and risk roles in AS morbidity, respectively.

Conclusions

The VDR gene TaqI polymorphism G allele may be a risk factor in AS susceptibility.

     

Association of Vitamin D Receptor Genetic Polymorphisms With Nephrolithiasis and End-Stage Renal Disease: A Meta-Analysis

BackgroundOur objective was to evaluate the association between vitamin D receptor (VDR) BsmI, FokI, TaqI, and ApaI gene polymorphisms and the risk of renal disease. A meta?analysis was conducted to determine the correlation between these VDR gene polymorphisms and the renal disease.MethodsMeta-analysis was carried out to clarify the association of BsmI (2467 cases and 2651 controls), FokI (2460 cases and 3085 controls), TaqI (3181cases and 3713 controls), and ApaI (2512 cases and 3091 controls) polymorphisms with nephrolithiasis (NL), diabetic nephropathy (DN), and end-stage renal disease (ESRD).ResultsThe VDR BsmI C allele, under the allele contrast random effect model, was associated with renal diseases calculated for ESRD. Subgroup analysis revealed association of VDR FokI polymorphism with ESRD and no association with NL and DN. The VDR TaqI C allele, under the allele contrast fixed effect model, was associated with renal diseases calculated collectively for DN, ESRD, and NL. Cochran's Q test showed no evidence of heterogeneity for TaqI and ApaI polymorphisms and showed a significant heterogeneity for BsmI and FokI polymorphisms.ConclusionsThis meta-analysis identifies BsmI, FokI, TaqI and ApaI polymorphisms of the VDR gene as risk factors for renal diseases.     

Association analysis of the polymorphisms of the <Emphasis Type="Italic">VDR</Emphasis> gene with bone mineral density and the occurrence of fractures

Associations of the FokI, BsmI, ApaI, and TaqI polymorphisms of the vitamin D receptor (VDR) gene with the bone mineral density (BMD) of the lumbar part of the spinal column (BMD LS) and the neck of the femur (BMD FN), and with the occurrence of fractures, were studied using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis on DNA isolated from peripheral blood of 239 women and 40 men from the region of western Poland. Three polymorphisms of the 3′ end of the VDR gene (BsmI, ApaI, TaqI) indicated a strong linkage disequilibrium. Association analysis of the VDR gene FokI polymorphism with BMD LS showed a dose effect of allele f. The association of the bAT haplotype of the BsmI, ApaI, and TaqI polymorphisms of the VDR gene with BMD FN was statistically significant. The association of the ApaI polymorphism with the occurrence of fractures was observed. Associations were also observed between the occurrence of fractures and the baT haplotypes of the VDR gene.     

The relationship of 3' vitamin D receptor haplotypes to urinary supersaturation of calcium oxalate salts and to age at onset and familial prevalence of nephrolithiasis.

BACKGROUND: Idiopathic hypercalciuria (IHc) and idiopathic hypocitraturia are frequently associated with calcium nephrolithiasis. We investigated the relationship of vitamin D receptor (VDR) polymorphisms (BsmI, TaqI and FokI) to urinary supersaturation of calcium oxalate salts in recurrent calcium oxalate stone formers with IHc and the clinical relevance of this relationship. METHODS: The study included 110 Caucasian stone formers with IHc and 127 unrelated healthy controls without history of nephrolithiasis. Age at onset of nephrolithiasis, familial history score (FHS) and the ion activity product of calcium oxalate salts in urine (AP(CaOx)) were tabulated. BsmI, TaqI and FokI VDR polymorphisms were evaluated in all participants. RESULTS: Patients and controls were classified as homozygous (bbTT and BBtt) or heterozygous in relation to BsmI and TaqI polymorphisms. Compared with BBtt patients, bbTT homozygous stone formers showed lower citrate excretion (1.91+/-0.89 vs 3.46+/-1.39 mmol/24 h, P = 0.004) and higher AP(CaOx) (2.02+/-0.51 vs 1.53+/-0.53, P = 0.006). Among controls, there were similar differences in citrate excretion and AP(CaOx) between the two groups, but they were not statistically significant. Compared with BBtt, bbTT patients showed lower mean age at onset of nephrolithiasis (29.7+/-12.1 vs 38.1+/-12.7 years, P = 0.008) and higher values of FHS (2.45+/-1.9 vs 0.83+/-0.7, P = 0.006). Similar results were obtained for individual BsmI and TaqI alleles. The analysis of FokI alleles was not informative. CONCLUSIONS: Recurrent calcium oxalate stone formers with IHc and the bT VDR haplotype have more aggressive kidney stone diseases as indicated by a higher familial incidence and lower mean age at onset. This clinical severity is associated with the higher urinary supersaturation of calcium oxalate salts and abnormalities of renal citrate handling.