维生素D受体基因多态性与铅作业工人血压的关系

目的 探讨维生素D受体(VDR)基因多态性与铅作业工人血压的关系。方法 选择216名职业铅接触工人，测定血铅、尿铅、尿ALA、尿肌酐和测量血压。采用限制性片段长度多态(RFLP)技术进行基因型分析。结果 VDR-bb,VDR-Bb和VDR-BB基因型的频率分别是90.7%,7.4%,1.8%.VDR-Bb/BB基因型的血铅几何均数（1.96μmol/L)高于VDR-bb基因型的血铅几何均数(1．54μmol/L)，P＜0．05。VDR—Bb/BB基因型工人的血铅与收缩压呈剂量-效应关系，回归系数为53．195(P＝0．003)，远大于不携带VDR-B等位基因(VDR-bb基因型)工人的回归系数(b＝5．512，P＝0．237)。结论 VDR-B等位基因可能与血铅水平和收缩压升高有关。     

儿童维生素D受体基因酶切位点多态性

目的：了解成都地区汉族人群VDR多态性分布情况,为进一步观察其与VDR遗传易感性疾病的相关性打下基础.方法：采用血清学方法,利用限制性内切酶TaqⅠ、ApaⅠ,应用聚合酶链反应（PCR）、限制性片段长度多态性（RFLP）分析、基因测序等技术,测定成都地区正常汉族儿童VDR基因多态性.结果：518名正常汉族儿童中TT、Tt、tt基因型分布频率分别为90.7%、9.1%、0.2%,T、t等位基因频率分别为95.3%、4.7%;AA、Aa、aa基因型分布频率分别为10.8%、36.7%、52.5%,A、a等位基因频率分别为29.2%、70.8%.结论：成都地区汉族儿童VDRTaqⅠ、ApaⅠ酶切位点多态性分布情况,与同属于蒙古人种的其它亚洲国家正常人群的分布频率相似;而与属于高加索人种的分布频率不同.     

维生素D受体基因多态性及维生素D水平与神经发育障碍关系的研究进展

维生素D及其受体在人体不同区域有广泛表达,后者介导活性维生素D的所有分子功能,其基因多态性已被证实与多种发育障碍类疾病易感性相关。现对维生素D受体基因多态性及维生素D水平与神经发育障碍关系的研究进行综述,以期为患儿临床早期预防、干预和治疗提供理论参考。     

维生素D受体基因多态性与儿童相关疾病的研究进展

<正>维生素D是一种固醇类衍生物,依赖维生素D受体(VDR)在人体中发挥广泛的生理功能。VDR能在多种组织和细胞中表达,由VDR基因编码。研究表明VDR与呼吸系统、免疫系统、心血管系统、血液系统、内分泌系统、神经系统及肿瘤等疾病的发生密切相关。VDR基因在人群中存在多态性分布,本文就VDR基因多态性与儿童相关疾病的研究做一综述。     

维生素D及其受体基因多态性与儿童疾病的相关性

人体内的维生素D源于肠道吸收及皮肤合成,属于脂溶性维生素,它不仅参与机体钙磷代谢的调节,还与内分泌、免疫、呼吸等多系统代谢调节相关。而维生素D受体及其基因多态性是维生素D在人体内发挥生物学效应的重要组成部分。本文就近些年来国内外关于血清维生素D水平、维生素D受体基因多态性与儿童呼吸、免疫等系统以及儿童生长发育、代谢等相关疾病的研究进行综述,为维生素D及其受体基因多态性在儿童疾病方面的研究及疾病的预防、治疗起到积极作用。     

维生素D受体基因多态性肿瘤易感性研究进展

随着遗传学、分子生物学等领域的不断发展．对肿瘤病因学的研究达到了分子基因水平。基因的多态性是指某一基因位点上存在着两个或两个以上不同的等位基因的现象，是造成个体对肿瘤易感性差异的重要因素。维生素D受体(vitaminiDreceptor，VDR)是介导1，25(OH)2D3发挥生物效应的核内生物大分子，为类固醇激素／甲状腺激素受体超家族的成员。1，25(OH)2D3是维生素D的活性形式，它除了具有经典的钙磷代谢调节作用外，还能调节多种正常或肿瘤组织细胞的生长和分化。本文针对近年来VDR基因多态性与肿瘤易感性的研究进展作一综述。     

上海市人群维生素D受体基因多态性频率分布调查

1 .材料与方法 :(1)标本来源 :选择本院体检或骨质疏松门诊的无亲缘关系的上海地区汉族居民 835人 ,男性 2 81人 ,女性 5 5 4人 ,年龄 4 2～ 93岁。(2 )白细胞ＤＮＡ提取 :取 1ｍｌ新鲜全血 (ＥＤＴＡ抗凝 ) ,加入 3ｍｌ溶血剂 (15 5ｍｍｏｌ ＬＮＨ4 Ｃｌ,10ｍｍｏｌ ＬＫＨＣＯ3,0 .1ｍｍｏｌ ＬＥＤＴＡ) ,10 %ＳＤＳ 10 0 μｌ及 10 μｌ蛋白酶Ｋ (2 0ｍｇ ｍｌ) ,置 5 6℃水浴过夜。随后 ,饱和酚 ,酚∶氯仿 (1∶1)和氯仿各抽提一次 ,最后水相中加入 2倍体积无水乙醇 ,0 .1倍体积 3ｍｏｌ ＬＮａＡｃ ,- 2 0℃ 2 0ｍｉｎ ,离心后 70 %乙…     

我国维吾尔族维生素D受体基因多态性分布的研究

目的研究我国乌鲁木齐维吾尔族妇女维生素D受体(VDR)基因多态性分布,探讨不同地区、不同民族之间基因型频率分布.为从VDR基因水平研究与骨质疏松的关系提供依据.方法采用聚合酶链反应(PCR)限制性片段长度多态性技术,对55例维吾尔族、179例汉族健康妇女进行VDR基因检测.结果维吾尔族55例中bb型40例(72.72%),Bb型12例(21.81%),BB型3例(5.45%),汉族179例,bb型162例(90.50%),Bb型17例(9.50%),未见BB型.结论中国维吾尔族VDR基因多态性分布与中国汉族比较,差异有显著性意义(P＜0.05).     

淄博市汉族育龄女性维生素D受体基因多态性分布

目的 针对淄博市汉族育龄女性开展分子流行病学调查,探讨维生素D受体(VDR)的基因多态性分布,获取淄博市的群体遗传学特征。方法 以2018年7月—2020年1月到淄博市中医医院进行围孕期检查的352名汉族健康女性为研究对象,采集口腔黏膜上皮脱落细胞,抽提基因组DNA,使用荧光定量PCR方法检测VDR Bsm I和Taq I位点基因多态性,进行统计分析。结果 (1)入组对象的基因多态性分布符合遗传平衡。(2)VDR Bsm I位点GG、GA及AA的基因型频率分别为89.2%、10.8%、0%,G、A等位基因频率分别为94.6%、5.4%。VDR Taq I位点TT、TC及CC的基因型频率分别为87.5%、12.5%及0.0%,T、C等位基因频率分别为93.8%、6.3%。(3)VDR Bsm I和Taq I两位点连锁有4种组合,频率从高到低依次是GG/TT(86.6%)、GA/TC(9.94%)、GG/TC(2.56%)及GA/TT(0.85%)。两位点间存在高度连锁不平衡(D’=0.915,r²=0.716)。结论 获取淄博市汉族女性VDR Bsm I、Taq I...     

维生素D受体基因多态性与食管癌易感性关系

目的探讨维生素D受体基因的多态性与食管癌易感性的关系。方法收集92例食管癌患者及115名对照，用聚合酶链反应-限制性片段长度多态性方法（PCR—RFLR），在维生素D受体基因的3’端分析限制性酶切位点TaqⅠ的多态分布。结果TaqI位点等位基因在2组间分布差异有统计学意义。与TT基因型者相比，Tt、tt基因型者患食管癌的危险性明显下降。结论维生素D受体基因的多态性与食管癌有关，Tt、tt基因型降低食管癌的易感性。     

Vitamin D receptor Fok1 polymorphism and blood lead concentration in children

Variation in blood lead concentration is caused by a complex interaction of environmental, social, nutritional, and genetic factors. We evaluated the association between blood lead concentration and a vitamin D receptor (VDR) gene polymorphism. Environmental samples and blood were analyzed for lead, nutritional and behavioral factors were assessed, and VDR -Fok1 genotype was determined in 245 children. We found a significant interaction between floor dust lead and genotype on blood lead concentration. For every 1 microg/ft(2) increase in floor dust, children with VDR -FF genotype had a 1.1% increase in blood lead [95% confidence interval (CI), 0.69-1.5], VDR -Ff, 0.53% increase (95% CI, 0.1-0.92), and VDR -ff, 3.8% increase (95% CI, 1.2-6.3); however, at floor dust levels < 10 microg/ft(2), children with VDR -ff had the lowest blood lead concentrations. These data suggest that VDR -Fok1 is an effect modifier of the relationship of floor dust lead exposure and blood lead concentration.     

Vitamin D receptor polymorphism among rickets children in Mongolia

BACKGROUND: It was reported that 32% of children under five years old in Mongolia had symptoms of rickets. Vitamin D receptor (VDR) gene polymorphism has received attention in relation to bone metabolism. We therefore investigated whether VDR polymorphism is related to high prevalence of rickets in Mongolia and to bone properties in childhood. METHODS: We conducted a case-control study in Ulaanbaatar involving 80 children aged 7-10 years with a history of rickets (cases) and 72 children with no history of rickets (controls). VDR polymorphism was assessed using BsmI, ApaI, and TaqI, and bone properties were determined by measuring age standardized tibial cortical speed of sound (TCSOS). FINDINGS: Each allelic frequency was verified to satisfy the Hardy-Weinberg equilibrium in cases, controls, and the total sample. The VDR polymorphisms among cases (BB 3%, Bb 18%, bb 80%; AA 15%, Aa 38%, aa 47%; and TT 81%, Tt 17%, tt 3%) did not differ significantly from those among controls (BB 1%, Bb 13%, bb 86%; AA 16%, Aa 46%, aa 38%; and TT 86%, Tt 13%, tt 1%). There were no significant differences in TCSOS according to the VDR genotype among either cases or controls. CONCLUSIONS: The VDR polymorphism does not play a major role in the development of rickets in Mongolia and has no effect on TCSOS in childhood.     

维生素D受体组合基因型与职业性铅毒性易感性的关系

目的 探讨维生素D受体(VDR)组合基因型与职业性铅作业者血铅浓度易感性的关系.方法 选取广州市职业病防治院铅作业工人专项体检中377名高暴露铅作业工人为研究对象,根据《中华人民共和国国家职业卫生标准》中《职业性慢性铅中毒诊断标准》(GBZ 37-2002),以血铅＜1.9 μmol/L者,为血铅正常组,血铅≥1.9 μmol/L者为血铅异常组.采用统一调查表问卷调查工人的基本情况:年龄、工龄、经济收入、吸烟、饮酒等.采用TaqMan探针技术对VDR基因Bs-mI、Tru9I和ApaI单核苷酸多态性(SNPs)进行检测,利用ABI7500 SDS Software V1.4软件,进行组合基因型的计算和构建.结果 高铅暴露人群中,VDR基因BsmI-Tru9I-ApaI的组合基因型中,与分布频率最高CC+ CC+ CC比较,CC+ CC+ AC是血铅浓度异常的危险因素,OR值为5.214(95％ CI 2.569～ 10.582),P＜0.01.结论 VDR基因BsmI-Tru9I-ApaI的组合基因型CC+ CC+ AC可能是铅中毒的易感基因型.     

Investigations of vitamin D receptor polymorphism affecting workers' susceptibility to lead

Gene polymorphism is an important factor that affects human susceptibility to toxins. For example, previous studies suggested that the ALAD genotype is an important factor affecting workers' susceptibility to lead toxic effects, including hemopoietic and nervous system. But we have had few researches in Taiwan, though there are thousands of workers involved in lead-related industries. On the other hand, although it is well known that lead deposits in the bone mineral component and interacts with calcium, vitamin D receptor may therefore be an important factor in the metabolism of lead. Some studies suggested that different vitamin D receptor genotypes have various kinds of receptor activity. The goal of this study was to investigate the polymorphism affecting workers' susceptibility to lead. Three allelic variants of the VDR gene were defined by means of the polymerase chain reaction (PCR) and three restriction enzymes (ApaI, BsmI, and TaqI). We determined the relationships of different VDR genotypes (AA, Aa, aa, BB, Bb, bb, TT, Tt, and tt) to blood lead and the index of cumulative blood lead levels (ICL). Altogether we analyzed 544 workers' VDR genotypes (BsmI, TaqI, and ApaI) and compared to their blood lead levels and ICL in the VDR genotypes. The results showed that workers had higher blood lead levels and ICL in the Apa I- aa genotypes, but this is not statistically significant when adjusted for potential confounding factors. Other characteristics, such as exposure status, smoking and alcohol drinking, were significantly associated with ICL and time-weighted ICL. Regression analyses suggested that exposure status and personal habits (smoking and alcohol drinking) are still the major effects on blood lead parameters for lead workers rather than genotypes. In conclusion, VDR genotypes did not significantly affect the long term blood lead parameters after adjustment for all factors, but industrial hygiene improvement, including engineering control and health education, are the most important ways to protect workers' health.     

Vitamin D3 improves lipophagy-associated renal lipid metabolism and tissue damage in diabetic mice

Oxidative stress and abnormal lipid metabolism in diabetes can trigger renal lipotoxicity, extending to diabetic nephropathy. Vitamin D₃ has been known to be involved in lipid metabolism as well as insulin secretion or inflammation. Therefore, we hypothesized that vitamin D₃ supplementation attenuated hyperglycemia-induced renal damage in diabetic mice. Diabetes was induced by a 40% kJ high-fat diet with 30 mg/kg body weight of streptozotocin by intraperitoneal injection twice in male C57BL/6J mice. Among diabetic mice (fasting blood glucose > 140 mg/dL), mice were supplemented with 300 ng/kg body weight of vitamin D₃ dissolved in olive oil for 12 weeks. Normal control and diabetic control mice were orally administrated with olive oil as a vehicle. Normal control mice were fed with an AIN-93G diet during the experiment. Vitamin D₃ supplementation in diabetic mice improved glucose intolerance and kidney function, demonstrated by diminishing glomerular areas. Vitamin D₃ supplementation in diabetic mice significantly reduced triglycerides and low-density lipoprotein cholesterol in plasma as well as triglycerides and total cholesterol in the kidney. Furthermore, vitamin D₃ supplementation attenuated lipid synthesis, oxidative stress, and apoptosis, accompanied by activation of β-oxidation, antioxidant defense enzymes, and autophagy in diabetic mice. In conclusion, vitamin D₃ supplementation ameliorates hyperglycemia-induced renal damage through the regulation of lipid metabolisms, oxidative stress, apoptosis, and autophagy in diabetes. Vitamin D₃ could be a promising nutrient to weaken diabetic nephropathy.     

铅中毒性肝病的临床特点和治疗体会

14例铅中毒性肝脏损害的病例均为中度铅中毒患者，其中急性铅中毒2例，亚急性铅中毒5例，慢性铅中毒7例，以ALT、AST升高为特征，多合并有尿中尿蛋白异常，预后良好，治疗的关键在于驱除体内的铅。     

Vitamin D receptor gene polymorphism and bone metabolism during low-dose oral contraceptive use in young women

With the aim to determine whether bone metabolism in young women using low-dose oral contraception is influenced by vitamin D receptor (VDR) genotype, we designed the prospective clinical study of 41 healthy women aged 20-27 years. Twenty-one women of the study group were prescribed an oral contraceptive (30 microg ethynyl estradiol and 150 microg levonorgestrel) and 20 women of the control group a nonhormonal contraceptive or none. Biochemical markers of bone metabolism (bone-specific alkaline phosphatase, osteocalcin, deoxypyridinoline) and VDR genotype, using BsmI endonuclease, were determined. After 3 months in the study group, the BB genotype subgroup showed significantly decreased osteocalcin (p = 0.010), in the Bb genotype subgroup bone-specific alkaline phosphatase (p = 0.043) and osteocalcin (p = 0.006) decreased, and in the bb genotype subgroup no changes were observed. In the control group, there were no significant changes in markers of bone metabolism regarding VDR genotype. In conclusion, our study shows that in young women VDR gene polymorphism could influence bone metabolism during low-dose oral contraceptive use.     

醋酸铅对小鼠免疫细胞增殖和DNA损伤的研究

目的探讨铅负荷对小鼠淋巴细胞DNA损伤及免疫毒性的影响。方法采用亚慢性铅染毒4周、10周的雄性小鼠80只,应用单细胞凝胶电泳技术(SCGE)、噻唑蓝(MTT)颜色反应及原子吸收石墨炉法检测胸腺、脾淋巴细胞DNA损伤,细胞增殖及胸腺、脾中铅含量。结果1.5、3.0、6.0g/L醋酸铅染毒4周均可导致小鼠胸腺、脾淋巴细胞DNA不同程度损伤,DNA迁移长度[胸腺(26.12±1.71)、(30.49±1.70)、(32.61±1.08)μm,脾(28.32±1.52)、(32.45±1.24)、(48.12±1.61)μm]均高于对照组[分别为(14.50±1.07)、(19.86±1.84)μm],差异有统计学意义(P<0.05)。3组浓度染毒10周的小鼠胸腺、脾淋巴细胞增殖转化功能增强,高剂量组胸腺脏器系数[(1.72±0.21)mg/g]及中、高剂量组脾脏器系数[分别为(6.66±0.06)、(7.18±0.10)mg/g]与对照组[分别为(1.21±0.17)、(3.82±0.05)mg/g]的差异有统计学意义(P<0.05)。3组胸腺、脾中铅含量随染毒剂量的增加而增加,与对照组相比,差异有统计学意义(P<0.05)。结论铅可致免疫细胞DNA单链断裂,淋巴细胞增殖。     

维生素D受体基因多态性对血铅及血清钙影响

目的探讨维生素D受体（VDR）基因多态性与接铅工人血铅和血清钙的关系。方法整群抽取成都市郊区某炼铁厂接铅作业人员112人,抽取其静脉血进行血铅、血清钙和基因多态性测定,按基因型测定结果分组分别比较其血铅、血清钙的差异,并进行血铅和血清钙的相关性分析。结果112名男性接铅工人中,99人（88.4%）为VDR-bb型,10人（8.9%）为VDR-Bb型,3人（2.7%）为VDR-BB;基因型的分布符合遗传学上的Hardy-Wein-berg平衡（P=1.0）。VDR-Bb/BB型的血铅高于VDR-bb型,但血清钙低于VDR-bb型。血铅和血清钙的相关性分析结果显示,VDR-bb型的相关系数r=-0.286,P=0.004;VDR-Bb/BB型的相关系数r=-0.451,P=0.122。结论维生素D受体基因多态性对接铅工人血铅和血清钙有一定影响。     

顺铂致小鼠肾损伤超微结构变化

目的：研究顺铂（DDP）所致肾毒性作用。方法：小鼠随机分为3组，阴性对照组、DDP组、分别给药处理后，取肾脏做病理组织学的光镜和电镜检查。结果：病理结果显示顺铂造成了小鼠肾结构的改变，主要表现为肾曲管上皮细胞浊肿，电镜结果显示，对照组呈现正常结构，DDP组曲管上皮细胞线粒体严重空泡化，嵴断裂；刷状缘微绒毛融合、破坏；基底皱纹消失；肾小球结构的足突部分融合，基底膜增厚走向紊乱，内皮细胞肿胀，模糊不清，间质纤维化，本次实验还发现顺铂可以使曲管内皮细胞水肿、模糊不清、此损伤国内未见报道。