转化生长因子-β1基因多态性及其血清水平与高血压病肾脏损害的关系

目的 探讨转化生长因子-β1(TGF-β1)基因 869T/C多态性和血清水平与高血压病(EH)及其肾脏损害的关系.方法 采用序列特异性引物聚合酶链反应(PCR-SSP),检测172例高血压病患者(其中90例伴有肾脏损害)及86例对照组TGF-β1基因 869T/C多态性,同时采用双抗体夹心ABC-ELISA法测定其血清TGF-β1水平.结果 高血压病肾脏损害组TGF-β1血清水平(50.36 ng/ml±6.92 ng/ml)显著高于高血压病无肾脏损害组(40.62 ng/ml±5.25 ng/ml)和对照组(39.52 ng/ml±6.68 ng/ml);高血压病肾脏损害组 869T/C位点TT、代及CC型频率分布(TT型13.3%、代型44.4%、CC型42.2%)与高血压病非肾脏损害组(TT型29.3%、TC型43.9%、CC型26.8%)及对照组(TT型32.6%、TC型44.2%、CC型23.2%)比较差异均有显著性;携带C等位基因个体EH肾脏损害的风险约是T等位基因的1.90倍(OR=1.90,95%CI:1.24～2.92);TT、TC、CC基因型组的TGF-β1血清水平(TT型36.32 ng/ml±3.05 ng/ml、TC型39.87 ng/ml±3.94ng/ml、CC型51.26 ng/ml±4.76 ng/ml)比较有显著性差异,其中CC基因型组明显高于其它两组.结论 TGF-β1基因 869T/C多态性通过影响TGF-β1的表达而与高血压病肾脏损害存在相关关系.     

转化生长因子β_1基因多态性与结直肠癌的关系

目的研究转化生长因子(TGF)-β1基因启动子-509C/T多态性与结直肠癌的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测118例结直肠癌患者和130例健康对照者TGF-β1的基因多态性,同时采用酶联免疫吸附试验(ELISA)检测血清TGF-β1水平。结果结直肠癌患者血清TGF-β1水平显著高于对照组〔(49.37±8.32)μg/L、(21.38±6.25)μg/L,P<0.01〕,而TGF-β1基因-509C/T多态性各等位基因及基因型频率在两组人群中的分布差异显著(P<0.05)。等位基因频率的相对风险分析发现,T等位基因携带者患结直肠癌的风险是C等位基因的1.759倍(OR=1.759,95%CI:1.150².691),携带T等位基因的结直肠癌患者血清TGF-β1水平显著高于不携带者〔(51.85±8.73)μg/L、(45.08±8.86)μg/L,P<0.01〕。结论 TGF-β1基因-509C/T多态性与结直肠癌的发病具有相关性,其中T等位基因可能是结直肠癌发病的遗传易感基因;携带T等位基因的个体可能通过促进TGF-β1的高度表达进而增加了结直肠癌的发病风险。     

转化生长因子β与高血压

研究表明转化生长因子β(TGF-β)是一基因家族编码产物,为多潜能生长因子,参与血管平滑肌细胞(VSMC)增殖、细胞外基质(ECM)沉积和血管重塑,并影响内皮素(ET-1)合成和肾素-血管紧张素系统(RAS)相互调节.因此,与高血压及其血管并发症关系密切.新近还发现TGF-β1的基因多态性与原发性高血压(EH)发病有关,而这一基因家族的其它成员与高血压的关系也渐受关注.     

转化生长因子β_1基因标签单核苷酸多态性与新疆汉族原发性高血压相关性研究

目的 研究转化生长因子β_1(TGF-β_1)基因标签单核苷酸多态(tSNP)及血浆水平与新疆汉族原发性高血压(EH)的关系,阐明连锁不平衡(LD)模式以及单体型分布特征.方法 采用整群抽取随机抽样的方式,以新疆沙湾县732例汉族人(EH组365例,对照组367例)为研究对象,进行流行病学调查和临床检查,并采集血样.用双抗体夹心法(ELISA试剂盒)测量TGF-β_1血浆浓度.SNaPshot方法进行基因分型.结果 (1)TGF-β_1基因rs11466345位点等位基因A、G在EH组和对照组中分布频率分别为69.7%、30.3%、74.4%、25.6%,EH组G等位基因频率高于对照组(x2=3.949,P=0.047),G等位基因患病风险为A等位基因1.261倍(95%CI 1.003～1.585,P=0.047),其他tSNP基因型及等位基因频率在EH组和对照组分布差异元统计学意义(P>0.05).(2)除m11466345位点外,其他tSNP位点间存在强LD,其构成的单体型频率在EH及对照组中分布差异无统计学意义(P>0.05).(3)TGF-β_1基因tSNP在EH组与对照组各基因型和等位基因之间TGF-β_1血浆水平差异无统计学意义(P>0.05).结论 TGF-β_1基因rs 11466345G等位基因可能是新疆汉族EH的遗传易感基因,其他tSNP可能与该民族EH不相关,除rs11466345位点外,其余tSNP位点间存在强LD,其构成的单体型与EH无关;在新疆汉族人群中TGF-β_1基因tSNP与TGF-β_1血浆水平不相关.     

上海地区汉族转化生长因子β基因多态性与高血压尿白蛋白的相关研究

目的探讨上海地区汉族人群转化生长因子β(TGFβ-)基因多态性与高血压尿白蛋白的关系。方法分别应用PCR-RFLP和等位基因专一PCR法,在352例高血压患者中确定TGF-β1T869C和TGFβ-3SS5608219多态性基因型;采用免疫速率散射比浊法测定24小时尿白蛋白(UAE)。结果高血压尿白蛋白组与尿白蛋白正常组之间T869C和SS5608219多态性基因型分布无显著差异(P>0.05)。在231例男性中,调整年龄、体重指数、收缩压和舒张压后,TGFβ-3AA基因型者UAE为39.0 mg/24h(P<0.05),显著高于AG(25.9 mg/24h,95%C I,19.7~34.1)及GG基因型者(22.0 mg/24h,95%C I,16.7~28.9);在121例女性中,不同基因型无显著性差异。结论在上海汉族男性高血压患者中,TGFβ-3SS5608219多态性与尿白蛋白相关。     

转化生长因子β1基因多态性及血清水平与高血压左室肥厚的关系

高血压是由遗传与环境因素相互作用而导致的多基因遗传病，左室肥厚（LVH）是病程中左室重塑的重要病理改变，包括心肌实质细胞肥大、间质纤维增生和血管重构，体内过量生成的转化生长因子β1（TGF-β1）被认为参与其中。近年来随着对TGF-β1的深入研究，发现其系一基因家族编码产物，其基因多态性与高血压左室肥厚的关系尚不清楚。我们检测其第10位密码子＋869T／C及第25位密码子＋915G／C单核苷酸多态性（SNP）在高血压患者和健康老年人中分布的差异，探讨基因型与表型之间的联系，以期为临床防治高血压及其并发症提供一定的实验依据。     

转化生长因子β_1基因标签单核苷酸多态性与新疆汉族原发性高血压相关性研究

Objective Essential hypertension (EH) was a complex disease resulted from the interaction of cumulative effect of multiple genetic and environment factors. The relationship between the genetic polymorphisms in the transforming growth factor-β_1 ( TGF-β_1 ), the blood levels and EH have been investigated, but the conclusions were different. Therefore, we investigate the relationship between the tagging single nucleotide polymorphisms (tSNPs) ( rs1800469, rs2241716, rs11466345, rs2241715,rs4803455) in TGF-β_1 gene, blood levels and EH in the Han nationality population in Xinjiang, to clarity the pattern of linkage disequilibrium (LD) and the feature of the structure of haplotype. Methods Based on the case-control study,we selected 732 (365 EH patients,367 controls) Han Chinese population from the Boertonggu countryside of Shawan region in the Xinjiang Uygur Autonomous Region of China by random cluster sampling. After questionnaire and physical examination, we collected blood samples, and the blood levels of TGF-β_1, were quantified using sandwich ELISA. The polymorphisms of TGF-β_1 gene in the study groups were detected with SNaPshot system. The case-control study in a large group was carried out separately for each of the tSNP and followed up by haplotypes analyses to determine the relation between tSNPs of TGF-β_1 gene and EH in the Han population. Results ( 1 ) The frequencies of alleles A, G of rs11466345 of TGF-β_1, gene in EH group and control group were as follows: 69.7%, 30. 3% ,74.4%,25.6%, respectively. It was demonstrated that the G allele of the rs11466345 polymorphism occurred at a significantly higher frequency in EH patients than in healthy controls (30. 3% vs. 25. 6%, P <0. 05). The rs11466345G-allele carriers had a significantly increased risk of EH compared to rs11466345A -allele carrier ( OR = 1. 261 ; P <0. 05). The frequencies of genotypes and alleles of the other tSNPs of TGF-β_1 gene had no difference between EH patients and controls ( P > 0. 05 ). (2) Except the site of rs11466345, the other tSNPs were in strong LD, and no statistical differences were observed in haplotypes distribution in the followup study between case-control groups (P >0. 05). (3) There were no difference of TGF-β_1 levels between the different genotypes and alleles in tSNPs of TGF-β_1 gene ( P > 0. 05 ). Conclusions ( 1 ) These results suggested that TGF-β_1 gene rs11466345 G allele was likely to be a genetic susceptibility factor for EH in the Xinjiang Han population, the other tSNPs perhaps had no association with EH of in the study groups. (2) Except rs11466345, the other tSNPs were in strong LD, and the haplotypes reconsreucted by tSNPs might not be associated with EH in the Han nationality populations. (3) There was no association between the tSNP of TGF-β_1 gene and TGF-β_1 blood levels in the Xinjiang Han nationality population.     

转化生长因子β_1基因标签单核苷酸多态性与新疆汉族原发性高血压相关性研究

Objective Essential hypertension (EH) was a complex disease resulted from the interaction of cumulative effect of multiple genetic and environment factors. The relationship between the genetic polymorphisms in the transforming growth factor-β_1 ( TGF-β_1 ), the blood levels and EH have been investigated, but the conclusions were different. Therefore, we investigate the relationship between the tagging single nucleotide polymorphisms (tSNPs) ( rs1800469, rs2241716, rs11466345, rs2241715,rs4803455) in TGF-β_1 gene, blood levels and EH in the Han nationality population in Xinjiang, to clarity the pattern of linkage disequilibrium (LD) and the feature of the structure of haplotype. Methods Based on the case-control study,we selected 732 (365 EH patients,367 controls) Han Chinese population from the Boertonggu countryside of Shawan region in the Xinjiang Uygur Autonomous Region of China by random cluster sampling. After questionnaire and physical examination, we collected blood samples, and the blood levels of TGF-β_1, were quantified using sandwich ELISA. The polymorphisms of TGF-β_1 gene in the study groups were detected with SNaPshot system. The case-control study in a large group was carried out separately for each of the tSNP and followed up by haplotypes analyses to determine the relation between tSNPs of TGF-β_1 gene and EH in the Han population. Results ( 1 ) The frequencies of alleles A, G of rs11466345 of TGF-β_1, gene in EH group and control group were as follows: 69.7%, 30. 3% ,74.4%,25.6%, respectively. It was demonstrated that the G allele of the rs11466345 polymorphism occurred at a significantly higher frequency in EH patients than in healthy controls (30. 3% vs. 25. 6%, P <0. 05). The rs11466345G-allele carriers had a significantly increased risk of EH compared to rs11466345A -allele carrier ( OR = 1. 261 ; P <0. 05). The frequencies of genotypes and alleles of the other tSNPs of TGF-β_1 gene had no difference between EH patients and controls ( P > 0. 05 ). (2) Except the site of rs11466345, the other tSNPs were in strong LD, and no statistical differences were observed in haplotypes distribution in the followup study between case-control groups (P >0. 05). (3) There were no difference of TGF-β_1 levels between the different genotypes and alleles in tSNPs of TGF-β_1 gene ( P > 0. 05 ). Conclusions ( 1 ) These results suggested that TGF-β_1 gene rs11466345 G allele was likely to be a genetic susceptibility factor for EH in the Xinjiang Han population, the other tSNPs perhaps had no association with EH of in the study groups. (2) Except rs11466345, the other tSNPs were in strong LD, and the haplotypes reconsreucted by tSNPs might not be associated with EH in the Han nationality populations. (3) There was no association between the tSNP of TGF-β_1 gene and TGF-β_1 blood levels in the Xinjiang Han nationality population.     

转化生长因子β1-509C／T基因多态性与大肠癌的关系

目的研究转化生长因子β1（TGF—β1）基因-509位点C／T的多态性,并探讨其与大肠癌易感性的关系。方法采用聚合酶链反应-限制性片段长度多态性方法,检测70例大肠癌组和102例对照组TGF—β1基因-509位点C／T等位基因及基因型分布,并对该基因多态性与大肠癌临床病理特征之间的关系进行分析。同时采用酶联免疫吸附试验（ELISA）检测大肠癌组和对照组血清TGF—β1水平。结果TGF—β1等位基因频率及基因型频率在大肠癌组和对照组的总体分布比较无显著性差异。大肠癌组按Dukes分期后,发现DukesC＋D期大肠癌患者-509CT／TT基因型频率明显高于DukesA＋B期患者（64．9％比39．4％,P=0．033,OR=2．840,95％CI：1．075～7．501）。DukesC＋D期大肠癌患者与DukesA＋B期相比,-509T等位基因频率有增高趋势（41．9％比27．3％,P=0．07,OR=1．922,95％CI：0．943～3．917）,但差异无显著性。大肠癌患者血清TGF—β1水平显著高于对照组。结论TGF—β1-509位点基因多态性与大肠癌无关,可能与大肠癌临床分期有关。     

转化生长因子β与高血压

研究表明转化生长因子β(TGF-β)是一基因家族编码产物，为多潜能生长因子，参与血管平滑肌细胞(VSMC)增殖、细胞外基质(ECM)沉积和血管重塑，并影响内皮素(ET-1)合成和肾素—血管紧张索系统(RAS)相互调节。因此，与高血压及其血管并发症关系密切。新近还发现TGF-β1的基因多态性与原发性高血压(EH)发病有关，而这一基因家族的其它成员与高血压的关系也渐受关注。     

转化生长因子β1基因多态性与乙型肝炎肝纤维化的关系研究

肝纤维化是慢性肝病发展到肝硬化的必经之路，阻断肝纤维化形成对改善肝硬化预后有重要意义。转化生长因子β1（TGF β1）是已知的最强的肝纤维化促进因子之一。临床上肝纤维化的形成具有一定的个体差异，这可能与患者的基因多态有关。Gewaltig等报道TGF β1＋869（T／C）、＋915（G／C）的多态性与丙型肝炎肝纤维化的发生有关，为明确TGF β1基因多态性与乙型肝炎肝纤维化的关系，进一步从基因水平上探讨、认识肝纤维化的发生机制，为今后肝纤维化基因治疗提供新的理论依据，我们选择＋869（T／C）、＋915（G／C）位点进行此项研究。     

转化生长因子β1和胰岛素样生长因子1与原发性高血压左室重构的关系

目的探讨转化生长因子β1(TGF-β1)、胰岛素样生长因子1(IGF-1)与原发性高血压(EH)左室重构的关系.方法EH组59例,对照组29例.同步检测血中TGF-β1、IGF-1、血管紧张素Ⅱ(AngⅡ)、醛固醇(ALD);用超声心动图仪测定并计算左室重量指数(LVMI).比较两组间上述指标的差异并分析EH组LVMI与其他指标的相关性.对相关的指标行Logistic回归分析.结果EH组血中TGF-β1水平较对照组降低(P＜0.01);AngⅡ、ALD水平均较对照组增高(P＜0.01).在EH组中,IGF-1及AngⅡ是左室肥大的独立危险因素(OR=1.008,1.081;P=0.020,0.020).结论EH患者左室重构与血中的IGF-1、AngⅡ水平有关,而与TGF-β1水平无关.     

转化生长因子β1与高血压肾损害的相关性研究

目的探讨转化生长因子β1(TGF-β1)与高血压肾损害发生发展的关系.方法将95例高血压患者根据其尿蛋白排泄率分为三组单纯高血压组35例;高血压微量蛋白尿组32例;高血压临床蛋白尿组28例.并与30例正常对照进行比较,采用双抗夹心酶联免疫法(FLISA)检测血清TGF-β1水平.结果高血压各组血清TGF-β1水平均高于正常对照组(P＜0.05),随着尿蛋白排泄率的增加,血清TGF-β1水平呈上升趋势,组间比较差异显著(P＜0.05);相关分析表明高血压各组血清TGF-β1水平与尿蛋白排泄率成正相关(r=0.51,(P＜0.01)),而与收缩压、舒张压水平不相关.结论高血压患者循环中TGF-β1水平明显升高,TGF-β1参与高血压肾损害的发生发展.     

转化生长因子-β1 T869C G915C基因多态性与特发性肺纤维化的相关性研究

目的研究转化生长因子-β1(TGF-β1)T869C、G915C基因多态性与特发性肺纤维化(IPF)的相关性。方法应用聚合酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP)检测2002年1月至2006年1月在首都医科大学附属北京朝阳医院住院确诊的47例IPF患者和47例年龄、性别、民族、吸烟情况匹配的对照者的TGF-β1T869C、G915C基因多态性。结果IPF组和对照组TGF-β1T869C基因型频率分布趋势不同,差异有显著性意义(P<0.05);2组中等位基因频率分布趋势相似,差异无显著性意义(P>0.05)。IPF组与对照组比较,TC基因型的OR值为0.421,95%CI为0.184~0.964,与IPF的发生呈显著负相关;而CC基因型的OR值为2.374,95%CI为1.038~5.433,与IPF的发生呈显著正相关。IPF组和对照组TGF-β1G915C基因的CC突变基因型与C等位基因频率均为0。结论TGF-β1 915位点基因多态性与IPF的发生可能无相关性,而TGF-β1 869位点的TC基因型和CC基因型可能与IPF的发生有关,提示有必要进一步扩大样本量进行TGF-β1 869位点基因多态性与IPF关联的相关研究。     

β1肾上腺素能受体Gly 389Arg多态性与原发性高血压的关系

目的:探讨汉族人群β1肾上腺素能受体Gly 389Arg多态性与原发性高血压的关系. 方法:采用聚合酶链反应-限制性长度片段多态性技术分析原发性高血压患者和正常人群β1肾上腺素能受体Gly 389Arg多态性.结果:高血压组Arg/Arg,Arg/Gly,Gly/Gly基因型频率分别为59.06%、35.09%、5.85%,正常对照组分别为43.55%、45.97%、10.48%;两组间三种基因型频率分布有统计学差异(x2=7.420,P＜0.05);高血压组Arg等位基因频率为76.61%,Gly等位基因频率为23.39%,正常对照组分别为66.53%、33.47%,两组间等位基因频率分布存在统计学差异(x2=7.299,P＜0.05);高血压组Arg纯合子基因型频率和Arg等位基因频率均明显高于对照组. 结论:β1肾上腺素能受体Gly 389Arg多态性可能与原发性高血压发病有关.     

转化生长因子-β1基因+869T/C位点多态性在心房颤动发生中的意义

目的研究转化生长因子β1(transforming growth factor-β1,TGF-β1)基因+869T/C多态性与心房颤动(房颤)发生的关系,探索TGF-β1基因+869T/C基因多态性在房颤发生中的意义。方法收集2006年9月至2008年11月心内科住院患者212例,根据有无房颤将患者分为房颤组103例,对照组109例,采用序列特异性引物聚合酶链反应检测TGF-β1基因+869T/C多态性。结果在房颤组中+869T/C位点的CC基因型频率高于对照组,差异有统计学意义(35%vs.19%,P0.05),+869C等位基因频率高于其对照组,差异有统计学意义(115%vs.90%,P0.05)。方差分析显示3种基因型的左心房直径差异有统计学意义[(36.54±6.34)mm vs.(39.93±7.70)mm vs.(40.48±7.96)mm;F=5.186,P=0.006],基因型与左心房直径间的关系为:TTTCCC。结论TGF-β1+869C基因型是房颤的易感基因型;同时携带TGF-β1+869C等位基因的人群更易患房颤。     

β_1肾上腺素能受体Gly389Arg多态性与原发性高血压的关系

目的探讨汉族人群β1肾上腺素能受体Gly389Arg多态性与原发性高血压的关系。方法采用聚合酶链反应-限制性长度片段多态性技术分析原发性高血压患者和正常人群β1肾上腺素能受体Gly389Arg多态性。结果高血压组Arg/Arg,Arg/Gly,Gly/Gly基因型频率分别为59.06%、35.09%、5.85%,正常对照组分别为43.55%、45.97%、10.48%;两组间三种基因型频率分布有统计学差异(χ2=7.420,P<0.05);高血压组Arg等位基因频率为76.61%,Gly等位基因频率为23.39%,正常对照组分别为66.53%、33.47%,两组间等位基因频率分布存在统计学差异(χ2=7.299,P<0.05);高血压组Arg纯合子基因型频率和Arg等位基因频率均明显高于对照组。结论β1肾上腺素能受体Gly389Arg多态性可能与原发性高血压发病有关。     

转化生长因子-β1及其基因多态性与慢性阻塞性肺疾病相关性的研究进展

慢性阻塞性肺疾病的发病率和死亡率在逐年升高,目前对其发病机制并未完全清楚,故对其发病机制的研究愈发重要.近年来的研究表明COPD是一种多基因调控的疾病.转化生长因子-β1(transforming growth factor-β1,TGF-β1)是一种多效性细胞因子,近年来倍受关注.研究认为,TGF-β1基因是COPD发生、发展的相关候选基因.现就TGF-β1的来源、分子结构、活化、信号转导、生物学功能、基因多态性及其与COPD相关性的研究进展进行概述.     

转化生长因子-β1基因多态性与 HBV 感染风险的相关性研究

目的：探讨转化生长因子-β1（ TGF-β1）基因多态性与中国人群HBV感染敏感性的关系。方法：本研究为以中国人群为研究对象的病例-对照研究,随机纳入50例HBV感染者（观察组）和50例与病例组性别、年龄相匹配的健康者（对照组）。采用聚合酶链反应-限制性片段长度多态性分析法检测TGF-β1基因T29 C多态性。结果：病例组和对照组基因型和等位基因分布均有明显差异（χ2＝12.795, df＝2, P＝0.002;χ2＝10.895, df ＝1, P＝0.002）。携带基因型TC和CC感染HBV的风险显著升高（ OR＝4.227,95％CI：1.604～11.139, P＝0.004; OR＝8.250,95％CI：2.042～33.334, P＝0.003）。携带等位基因C较等位基因T感染HBV的风险显著升高（ OR＝2.631,95％CI：1.472～4.702, P＝0.001）。结论： TGF-β1基因T29C多态性可能与HBV感染风险有关。     

转化生长因子β1与慢性阻塞性肺疾病关系的研究进展

慢性阻塞性肺疾病(COPD)近年来发病率和病死率呈上升趋势,目前对其发病机制尚未完全明确,其发病机制的探索显得格外重要.转化生长因子β1(transforming growth factor β1,TGF-β1)是一个多功能的细胞因子,近年来格外受到关注.研究表明,TGF-β1与COPD发生发展有着重要的联系,现在就TGF-β1的结构、生理功能、吸烟、基因多态性、肺功能及其与COPD相关性的研究进展进行概述.