维生素D受体起始密码子基因多态性与系统性红斑狼疮相关性研究

目的 检测维生素D受体(VDR)基因多态性在系统性红斑狼疮(SLE)患者中的分布,探讨其与SLE发病的相关性.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测VDR起始密码子(FokI)多态性位点和基因型在271例SLE患者和130名健康对照组中的分布情况.采用χ2检验和方差分析进行统计学处理.结果 SLE患者及健康对照组VDR FokI多态性基因型和等位基因分布均不处于Hardy-Weinberg平衡(SLE组χ2=7.883,P=0.019;健康对照组:χ2=7.288,P=0.026).VDR FokI多态性等位基因F和f的分布频率在健康对照组分别为48.8%和51.2%,在SLE组分别为60.9%(χ2=10.39,P=0.001)和39.1%(χ2=10.39,P=0.001);F等位基因个体发生SLE的比值比(OR)为1.630(95%CI=1.210～1.1%,χ2=10.39,P=0.001).基因型FF、Ff和ff分布频率在健康对照组中分别为25.4%、46.9%和27.7%,在SLE组中分别为42.8%(χ2=11.417,P=0.001)、36.2(χ2=4.251,P=0.039)和21.0%(χ2=2.187,P=0.139);FF和Ff基因型个体发生SLE的OR分别为2.200(95%CI=1.385～3.493,χ2=11.417,P=0.001)和0.641(95%C1=0.419～0.979,χ2=4.251,P=0.039).进一步分析发现,不同VDR FokI多态性基因型SLE患者之间疾病活动性积分(SLEDAI)差异无统计学意义(P=0.382).但与FF和ff基因型SLE患者对照,Ff基因型SLE患者中浆膜炎的发生率更高(P=0.001),而且具有更高阳性率的抗双链DNA(dsDNA)抗体(P=0.001)、抗Sm抗体(P=0.047)和抗组蛋白抗体(P=0.001),但皮疹发生率较低(P=0.005).结论 VDR FokI多态性位点F等位基因和F/F及F/f基因型与SLE发病易感性有关,而且F/f杂合子患者更容易发生浆膜炎和产生抗dsDNA抗体、抗Sm抗体和抗组蛋白抗体.     

初治肺结核患者维生素D与其受体基因多态性位点FokI的相关性分析

目的分析初治肺结核患者血清维生素D(VD)与维生素D受体(VDR)基因多态性位点Fok I的相关性。方法对我院随机选取的180位初治肺结核患者和100位正常对照的血清VD水平,VDR基因多态性位点Fok I基因型进行检测,比较和分析2组血清VD水平与VDR基因Fok I多态性差异以及相关性。结果初治肺结核患者血清VD水平明显低于正常对照组(P0.0001);初治肺结核组VD营养缺乏率(70.5%)明显高于正常对照组(47.0%),VDR基因多态性位点Fok I的三种基因型(纯合子FF,纯合子ff和杂合子Ff)在两组内的分布差异具有统计学意义(P=0.033),初治肺结核组纯合子ff及等位基因f比率明显高于正常对照组(P0.05);初治肺结核患者基因型ff组VD水平明显低于基因型FF组和基因型Ff组(P0.05)。结论初治肺结核患者血清VD水平明显下降,VDR基因多态性位点Fok I基因型ff为肺结核易感基因。     

VDR起始密码子区突变与北方汉族人群乳腺癌易感性的关系研究

目的探讨维生素D受体（VDR）起始密码子区FokⅠ突变与中国北方汉族人群乳腺癌发病的相关性。方法提取81例乳腺癌患者及78例健康对照者外周血基因组DNA（gDNA）,应用聚合酶链反应—限制性片段长度多态性检测并分析DNA FokⅠ多态性在两组中的分布。结果健康对照组FokⅠ多态位点FF、Ff、ff基因型频率,等位基因F、f分布频率分别为33.33%、56.41%、10.26%、61.5%、38.5%;病例组分别为19.75%、59.26%、20.99%、49.4%、50.6%,组间比较均有统计学差异（P均〈0.05）。Ff、ff基因型人群乳腺癌患病风险的OR值分别为1.30和1.84（P均〈0.01）。结论 VDR等位基因f有可能成为乳腺癌的遗传标志基因。     

维生素D受体基因多态性与结核易感性关系的荟萃分析

目的 应用荟萃分析探讨维生素D受体(VDR)基因FokI、TaqI多态性与结核易感性的关系.方法 在中国知网(CNKI)、中国生物医学文献数据库(CBM)、万方数据资源系统、MEDLINE和PubMed中,应用关键词"结核"、"基因多态性"或"遗传多态性"、"等位基因"、"VDR"、"tuberculosis"或"alleles"搜索1980年1月至2007年11月发表的相关中英文文献,最终入选文献14篇.应用RevMan4.2软件包分别对14项研究结果进行数据分析.结果 荟萃分析计算得出合并OR值(95%CI):Ff/FF基因型为1.12(0.98～1.28),ff/FF基因型为1.66(1.12～2.46),Tt/TT基因型为0.97(0.82～1.14),tt/TT基因型为1.27(0.96～1.69).计算FokI基因的失安全系数为109.69,TaqI基因的失安全系数为75.24,说明分析结果可靠.结论 维生素D受体基因FokI多态性与结核易感性有关,TaqI多态性与结核易感性尚无明确关系.     

维生素D受体基因多态性与新疆维吾尔族人群结核病易感性的相关性研究

目的研究维生素D受体(VDR)基因多态性与新疆维吾尔族人群结核病易感性的相关性。方法采用病例对照研究,选取224例新疆维吾尔族结核患者和225例有分枝杆菌感染史的同民族健康者分别作为病例组和对照组。用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)分析方法分别检测维生素D受体基因的多态性,内切酶分别为FokI和TaqI,并进行基因分型。统计学分析结果采用χ2检验,P值为0.05。结果FokI分析,分为FF、Ff、ff三种基因型,其在病例组和对照组中分别为36%、57%、7%和40%、54%、6%。FF基因型的分布在病例组与对照组中的差异性无统计学意义(χ2=0.872,P>0.05)。TaqI分析,分为TT、Tt、tt三种基因型,其在病例组和对照组中分别为68.8%、29.4%、1.8%和75.6%、22.2%、2.2%。TT基因型在病例组与对照组中的差异性也无统计学意义(χ2=2.588,P>0.05)。结论维生素D受体基因中FokI与TaqI多态性与新疆维吾尔族人群结核病易感性无明显相关性。     

内蒙古地区老年女性维生素D受体基因Fok1多态性与骨质疏松的关系

目的 探讨维生素D受体(VDR)基因Fok1多态性与内蒙古地区汉族老年女性骨质疏松(OP)的关系.方法 应用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP),对70例对照者和32例OP患者的VDR基因Fok1多态性进行分析,并分别计算两组人群Fok1基因型和等位基因的分布频率.结果 对照组人群Fok1多态性FF、Ff、ff基因型的分布频率分别为38.57%、50%、11.43%.OP组分别为21.88%、43.75%、34.37%.两组人群基因型的分布频率差异有显著性(χ2=8.211,P<0.05).结论 老年女性VDR基因Fok1多态性与OP相关.     

维生素D受体基因多态性与慢性乙型肝炎的相关性

目的探讨维生素D受体（VDR）基因多态性与慢性乙型肝炎的相关性。方法以53例慢性乙肝患者和56例健康人为研究对象,应用聚合酶链反应-限制性片段长度多态性方法分析VDR基因FokⅠ和BsmⅠ酶切位点的多态性。两组间基因型比较采用x^2检验。结果53例慢性乙肝患者中,BB、Bb、bb基因型频率分别为9．4％、20．8％、69．8％,其中BB基因型频率高于正常对照组,差异有统计学意义（P〈0．05）。B等位基因频率在慢乙肝组为19．8％显著高于正常对照组8．9％（P〈0．05）。病例组中FF、FT、ff基因型频率分别为32．1％、52．8％、15．1％,与正常对照组无统计学差异。F等位基因频率在慢乙肝组为58．5％,与正常对照组差异无统计学意义。结论VDR基因多态性与HBV感染有关,特别是Bsml酶切位点多态性可增加慢性HBV感染。     

维生素D受体基因多态性与黎族老年骨质疏松的易感性

目的探讨维生素D受体基因(VDR)多态性(rs11568820,Fok I酶切位点;rs1544410,Bsm I酶切位点)与黎族老年骨质疏松的易感性。方法入选118例骨质疏松患者和140例健康对照人群,采用美国双能X线测量仪检测BMD,限制性片段长度多态性分析(RFLP)技术检测Fok I和Bsm I酶切位点多态性。结果全部标本中,FF、Ff、ff基因型分布频率为57.8%、37.2%、5.0%,BB、Bb、bb基因型分布频率为17.4%、45.0%、37.6%。携带Ff基因型患骨质疏松风险是携带FF基因者的1.13倍,携带ff基因型患骨质疏松风险是携带FF基因型者的1.64倍;相比于Fok I多态性位点,携带Bb基因型患骨质疏松风险是携带BB基因者的1.87倍,携带bb基因型患骨质疏松风险是携带BB基因型者的4.21倍,风险更高。结论 Fok I和Bsm I酶切位点多态性与老年骨质疏松易感相关。     

帕金森病患者维生素D受体基因多态性及血清25-羟维生素D水平变化观察

目的 观察帕金森病（PD）患者维生素D受体（VDR）基因多态性和血清25-羟维生素D(25(OH)D)水平变化,分析二者与PD发病的相关性及对PD发病的预测效能,以明确VDR基因多态性及血清25(OH)D水平与PD发病的关系。方法 纳入178例PD患者（PD组）及同时期185例体检健康者（对照组）。采用PCR法和DNA测序法检测VDR基因FokⅠ（rs2228570）和BsmⅠ（rs1544410）位点的基因分型,采用酶联免疫吸附法检测外周血清25(OH)D,对两组上述指标进行比较。采用多因素Logistic回归分析PD发病独立危险因素;ROC分析维生素D受体基因多态性和血清25-羟维生素D水平对PD发病的预测效能。结果 PD组FokI位点T等位基因与TT基因型频率分别为48.6%、25.3%,对照组分别为37.7%、15.1%,两组比较,χ2分别为8.516、10.383,P分别为0.004、0.001。PD组BsmⅠ位点各等位基因及基因型与对照组比较差异均无统计学意义（P均>0.05）。PD组血清25(OH)D水平为（16.06±6.04）ng/mL,对照组为（19.22±6...     

新疆维吾尔族人群胃癌与维生素D受体基因FokⅠ多态性的相关性

目的:探讨维生素D受体基因FokⅠ酶切位点多态性与胃癌的相关性.方法:随机选取2013-03/2015-05新疆肿瘤医院就诊的维吾尔族胃癌患者147例(A组)及维吾尔族健康对照者151例(B组),采用多聚酶链反应-限制性酶切片段长度多态性方法测定维生素D受体基因FokⅠ酶切位点多态性,进行两组间比较;将本研究全部胃癌患者经PCR-RFLP测定后按是否带有f基因分为FF组(a组)与Ff+ff组(b组),进行组间D-二聚体测定水平比较.结果:胃癌患者的f等位基因表达频率高于对照组(57.8%vs 47.4%,P0.05).多因素分析显示:含f等位基因(Ff+ff)的研究对象患胃癌的风险高于不含f等位基因(FF)的研究对象(OR=2.85);含f等位基因组中D-二聚体测定水平较不含f等位基因组明显升高(2.79±1.21 vs 1.09±0.65,P0.05);随胃癌患者分化严重程度的逐步加重,单纯含F基因(FF)的患者的比例逐步下降(P0.05).结论:维生素D受体基因FokⅠ酶切位点多态性与维吾尔族胃癌易感性相关联,f等位基因可能是维吾尔族胃癌发生的危险因素之一,而F位点可能是维吾尔族胃癌发生的保护因素.f等位基因可能是调节D-二聚体水平的因素之一,从而影响了维吾尔族胃癌患者的发生或预后.     

新疆哈萨克族人群结核病易感基因的病例对照研究

目的研究自然抗性相关巨噬细胞蛋白1(NRAMPl)基因3′端非编码区(3′UTR)和维生素D受体(VDR)基因FokI、TaqI位点多态性与新疆哈萨克族人群结核病易感性的关联;分析NRAMPl基因和VDR基因交互作用对新疆哈萨克族人群结核病易感性的影响。方法采用病例对照研究方法,选取新疆哈萨克族活动性肺结核病患者213例,同地区同种族健康者211例。用聚合酶链反应 限制性片断长度多态性(PCR RFLP)分析方法对NRAMP1基因3′UTR、VDR基因FokI和TaqI多态性位点基因分型,采用χ2检验分析3个位点多态性与新疆哈萨克族结核病易感性的关系,相乘模型分析NRAMPl基因和VDR基因交互作用。结果1. NRAMPl基因3′UTR位点在病例组和对照组中TGTG/TGTG、TGTG/del和TGTGdel/del基因型频率分别为64.8%、29.6%、5.6%和79.1%、19.5%、1.4%。TGTGdel等位基因组间分布差异有统计学意义(χ2=13.737,P<0.01)。2. VDR基因FokI位点在病例组和在对照组中FF、Ff和ff基因型频率分别为33.8%、45.1%、21.1%和47.9%、41.7%、10.4%。f等位基因频率组间分布差异有统计学意义(χ2=13.868,P<0.01);TaqI位点TT、Tt和tt基因型组间分布差异无统计学意义;等位基因T和t组间分布差异无统计学意义(χ2=1.267,P>0.05);D'=0.477,r2=0.01,两位点不存在连锁不平衡。3. NRAMP1基因和VDR基因存在正交互作用,ORint=1.62。结论1. TGTG/del和TGTGdel/del基因型、TGTG缺失等位基因可能是新疆哈萨克族人群结核病易感基因。2. VDR基因中FokI多态性与新疆哈萨克族结核病易感性有关联,等位基因f可能是新疆哈萨克族结核病易感基因。3. NRAMP1和VDR基因间交互作用可能增加新疆哈萨克族人群结核病的发病风险。     

Association between vitamin D receptor FokI. Polymorphism and serum parathyroid hormone level in patients with chronic renal failure

We investigated the relationship between vitamin D receptor (VDR) start codon polymorphism and serum levels of PTH, calcidiol, and calcium in 64 Spanish patients with chronic renal failure (CRF). An exon 2 fragment of the VDR gene was amplified by PCR, and cleaved with the restriction enzyme FokI. The alleles were identified according to the digestion pattern obtained as F (absence of restriction site) and f (presence of restriction site). Genotype frequencies in the patient population were 54.7% FF, 28.1% Ff and 17.2% ff, vs 46.7% FF, 43.3% Ff and 10% ff in a healthy control population. The difference between the two populations was statistically significant (p<0.01). Within the patient population, mean serum PTH level in the FF group was significantly higher (159.77+/-25.69 pg/ml) than in both the Ff and ff groups (106.67+/-19.07 and 77.55+/-15.85 pg/ml, respectively; p<0.05). However there were no significant differences in serum levels of calcidiol or calcium among genotypes. These results suggest that FokI polymorphisms of the VDR gene may determine parathyroid response in CRF patients.     

Vitamin D receptor polymorphisms (FokI, BsmI) and breast cancer risk: association replication in two case-control studies within French Canadian population

Vitamin D has been associated with reduced breast cancer risk. We studied the association of two vitamin D receptor (VDR) gene single nucleotide polymorphisms restriction enzyme detecting SNP of VDR (FokI and BsmI) with breast cancer risk in two independent case-control studies carried out in the same population. The modifying effect of family history of breast cancer on this relationship was also evaluated. The first and second studies included respectively 718 (255 cases/463 controls) and 1596 (622 cases/974 controls) women recruited in Quebec City, Canada. FokI and BsmI genotypes were assessed. Relative risks of breast cancer were estimated by multivariate logistic regression. Compared with homozygotes for the common F allele (FF genotype), FokI ff homozygotes had a higher breast cancer risk (study 1: odds ratio (OR)=1.22, 95% confidence interval (CI)=0.76-1.95; study 2: OR=1.44, 95% CI=1.05-1.99; and combined studies: OR=1.33, 95% CI=1.03-1.73). Significant interactions were observed between FokI and family history of breast cancer in the two studies as well as in the combined analysis (P interaction=0.031, 0.050 and 0.0059 respectively). Among women without family history, odds ratios were 1.00, 1.27 (95% CI=1.02-1.58) and 1.57 (95% CI=1.18-2.10) respectively for FF, Ff and ff carriers (P(trend)=0.0013). BsmI Bb+bb genotypes were associated with a weak non-significant increased risk in the two studies (combined OR=1.22, 95% CI=0.95-1.57) without interaction with family history. Results support the idea that vitamin D, through its signalling pathway, can affect breast cancer risk. They also suggest that variability in observed associations between VDR FokI and breast cancer from different studies may partly be explained by the proportion of study subjects with a family history of breast cancer.     

Vitamin D receptor genotype is associated with fat-free mass and sarcopenia in elderly men

We investigated the association of vitamin D receptor (VDR) genotype with fat-free mass (FFM) in a cohort of 302 older (aged 58-93 years) Caucasian men who underwent body composition analysis by dual-energy X-ray absorptiometry, and completed questionnaires addressing comorbidities, physical activity, and dietary intake. All participants were genotyped for a VDR translation start site (FokI) polymorphism [FF (37.7%), Ff (48.4%), and ff (13.9%)] and the previously studied BsmI polymorphism [BB (24.9%), Bb (37.7%), and bb (37.4%)]. The BsmI polymorphism was not associated with FFM in any analysis; however, the FokI polymorphism was significantly associated with total FFM, appendicular FFM, and relative (kg/m(2)) appendicular FFM (all p <.05), with the FF group demonstrating significantly lower FFM than the Ff and ff groups (e.g., total FFM: FF = 57.6 +/- 0.4, Ff = 59.4 +/- 0.4, ff = 59.4 +/- 0.7 kg; p <.02). Age-adjusted logistic regression revealed a 2.17-fold higher risk for sarcopenia (defined previously as appendicular FFM <7.26 kg/m(2)) in FF homozygotes (95% CI [confidence interval] = 1.19-3.85; p =.03) compared to men with one or more f alleles. The VDR translation start site (FokI) polymorphism is significantly associated with FFM and sarcopenia in this cohort of older Caucasian men.     

Serum parathyroid hormone levels are associated with FokI polymorphism of the vitamin D receptor gene in untreated postmenopausal women

BACKGROUND: Allelic variants in polymorphisms of the vitamin D receptor (VDR) gene have been related to the incidence of secondary, as well as primary, hyperparathyroidism. In spite of their pathophysiological importance, the relationships between VDR genotypes and serum PTH regulation in normal women have not been extensively investigated. METHODS: We studied the association between the VDR gene (FokI polymorphism) and serum parathyroid hormone (PTH) levels during the winter in 95 untreated, postmenopausal women with normal values of serum PTH. We checked statistically for years since menopause (YSM) and serum ionized calcium. Intergroup differences in serum PTH levels between FF, Ff, and ff allele combinations of FokI polymorphism were evaluated using a one-way ANCOVA and the least significant difference (LSD) multiple comparisons test. RESULTS: Significant intergroup differences were found in PTH values (P<0.035, ANCOVA), which were higher in the ff than in the FF genotype (P<0.01, LSD). No differences in serum PTH were found between allele combinations in ApaI, TaqI, and BsmI polymorphisms. CONCLUSION: Our findings suggest that the FokI polymorphism of the VDR gene is closely related to the magnitude of PTH secretion and/or degradation in postmenopausal women. The causal importance of this phenomenon in the development of postmenopausal osteoporosis remains to be determined.     

Vitamin D receptor gene start codon polymorphism (FokI) and bone mineral density in healthy male subjects

OBJECTIVE: The genetic factors determining peak bone mineral density (BMD) in men are not well characterized. Recent studies have investigated the relationship between the start codon polymorphism (SCP) of the vitamin D receptor (VDR) gene and BMD in different populations. We have now examined the relationship between SCP of the VDR gene and BMD in a group of healthy Caucasian men from the north-east of England. SUBJECTS: Ninety-six healthy men (median age 50, range 40.0-77.0 years). MEASUREMENTS: Analysis of the FokI genotypes of SCP of the VDR and measurements of BMD at the femoral neck and lumbar spine were performed. RESULTS: FF, Ff and ff VDR FokI genotypes were found to have the highest, intermediate and the lowest lumbar spine BMD, respectively (Mean +/- SD, for FF 1.07 +/- 0.14, Ff 1.05 +/- 0.16 and ff 0.95 +/- 0.10 g/cm2). There was a significant difference in spine BMD between FF and ff genotypes (P < 0.05, analysis of variance [ANOVA]), but no such difference was apparent between Ff and ff (P > 0.05, ANOVA). Interestingly, there was no association between FokI polymorphism and femoral neck BMD (Mean +/- SD, for FF 0.85 +/- 0.12, Ff 0.87 +/- 0.15 and ff 0.83 +/- 0.15 g/cm2). The distribution of FokI VDR genotypes approached Hardy-Weinberg equilibrium and was similar to that reported for women from different ethnic groups, as the prevalence of FF and ff genotypes was 44% and 16%, respectively. CONCLUSION: The study shows that in this population of healthy men there is a weak association between lumbar spine bone mineral density and FokI restriction fragment length polymorphism at the translation initiation site of the vitamin D receptor gene.