CCND1基因A870G多态与结直肠癌遗传易感性的相关性

目的:探讨CCND1基因A870G多态与上海地区人群结直肠癌(colorectal cancer, CRC)遗传易感性的关系.方法:采用TaqMan MGB探针实时定量PCR法.检测104例CRC与205名对照人群CCND1A870G基因型分布及差异.结果:CRC组和对照组870A等位基因频率分别为60.1%和52.4%,A的CRC发病风险是G的1.40倍(95%CI=0.99-1.97,P=0.057).与GG基因型相比,GA基因型的CRC风险增加至1.99倍(95%CI=0.94-4.20,P=0.070),而AA基因型的CRC风险显著增加至2.46倍(95%CI=1.09-5.56,P=0.031).将GA、AA基因型合并计算,则其CRC发病风险与GG基因型相比呈相似的显著性增加(OR=2.13,95%CI=1.03-4.39,P=0.040).结论:CCND1 870A增加CRC发病风险,可作为这一地区CRC高危人群的筛选指标.     

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。     

hOGG1基因多态与结直肠癌和肝细胞癌遗传易感性

目的探讨hOGG1基因第326密码子多态（Ser326Cys）与中国人群结直肠癌（CRC）和肝细胞癌（HCC）遗传易感性的关系。方法采用TaqMan方法检测345例CRC与670例对照以及175例HCC与119例对照的hOGG1Ser326Cys基因型分布及差异。结果总体上，hOGG1 Ser326Cys基因型分布在HCC-对照、CRC-对照以及不吸烟的CRC-对照人群间均无显著性差异（P〉O．05）。但在吸烟人群中，326Cys是CRC发生的危险因素（OR=1．58，95％CI=1．14～2．19，P=0．006）；与Ser／Ser基因型及Ser等位基因携带者（Ser／Ser、Ser／Cys基因型）相比，Cys／Cys基因型的CRC风险显著增加至2．40倍（95％CI=1．20～4．78，P=0．013）及2．02倍（95％CI=1．21-3．37，P=0．008）。结论hOGG1Ser326Cys多态可能与HCC发病风险无关，但Cys／Cys基因型增加中国吸烟人群的CRC发病风险。     

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β1-509C/T基因多态性与冠心病遗传易感的相关性分析

目的探讨中国汉族人群转化生长因子(TGF)-β1-509C/T基因多态性与冠心病遗传易感的关系。方法选择冠心病患者340例为冠心病组,非冠心病患者271例为对照组,利用聚合酶链反应连接酶检测反应分析技术对TGF-β1-509C/T(rs1800469)多态位点进行分型,采用非条件logistic回归分析统计该多态位点与冠心病易感的相关性。结果冠心病组与对照组CC、CT和TT基因分布比较,差异无统计学意义,-509C/T多态位点与冠心病无易感相关性(χ2=2.813,P=0.245)。在不吸烟患者中,CT和TT基因型均显著增加个体患冠心病的风险(OR=1.98,95%CI:0.98～4.02,P=0.059、OR=2.49,95%CI:1.20～5.17,P=0.014),T等位基因明显增加个体患冠心病的发病风险(OR=1.49,95%CI:1.07～2.08,P=0.019)。结论 TGF-β1-509C/T(rs1800469)多态位点在不吸烟人群中与冠心病的遗传易感有关,并且T等位基因是个体患冠心病的危险因素。     

亚甲基四氢叶酸还原酶基因C677T多态与结直肠癌遗传易感性的相关性

目的:探讨亚甲基四氢叶酸还原酶基因(MTHFR)C677T多态与结直肠癌(CRC)遗传易感性的关系.方法:采用TaqMan方法检测CRC 449例与对照672例的MTHFR C677T的基因型分布及差异.以非条件Logistic回归法计算表示相对危险度的比值比(OR)及其95%可信区间(CI).OR值均经性别、年龄、吸烟、饮酒、体质量指数和一级亲属CRC家族史等因素校正.结果:CRC组677T等位基因频率显著低于对照组,其为CRC发生的保护因素(OR:0.70,95%CI:0.58-0.83,P<0.01).与CC纯合子相比,CT杂合子的CRC风险显著降低至0.73倍(95%CI:0.56-0.95,P<0.05),而TT纯合子的CRC风险进一步降至0.47倍(95%CI:0.33-0.68,P<0.01).在非饮酒人群中,C677T的CRC风险保护效应略有增强;而在饮酒人群中,CT和TT基因型携带者的CRC发病风险虽仍低于CC基因型携带者,但差异无统计学意义.在CRC人群中,荷大肿瘤(最大直径>4cm)者携带TT基因型的比例高于荷小肿瘤者(16.3% vs 8.3%,P<0.05);荷黏液腺癌者携带TT基因型的比例高于荷乳头状腺癌及管状腺癌者(22.2% vs 17.1%,10.3%,P=0.084).结论:MTHFR C677T降低CRC发病风险,饮酒可能削弱该多态的CRC风险保护效应.TT基因型可能与CRC肿瘤进展有关.     

转化生长因子-β1在结直肠癌中的表达及与预后的关系

目的探讨转化生长因子（TGF）-β1在结直肠癌中的表达水平及与预后的关系。方法应用免疫组化技术检测52例结直肠癌病例术后标本巾TGF-β1表达水平与血管内皮生长凶子（VEGF）及临床病理特征间的相关性，Log-rank时序检验TGF61蛋白表达与生存时间的关系。结果TGF-β1表达为阴性和阳性者分别有11例和41例，而VEGF表达为阴性和阳性者分别有14例和38例，两者间有显著相关性（X^2=0．633，P〈0．01），TGF-β1表达与Dukes分期（X^2=19．866，P〈0．01）、淋巴结转移情况（X^2=13．152，P〈0．01）也显著相关。本组病例总的3年生存率为49．1％，而TGF61表达为阴性和阳性者的3年生存率分别为69．2％和20．5％（X^2=11．64，P〈0．01）。结论TGF-β1表达水平是影响结直肠癌患者预后的重要因素，临床上作为判断患者预后指标值得进一步研究。     

亚甲基四氢叶酸还原酶基因C677T多态与肝细胞癌遗传易感性的相关性研究

目的探讨亚甲基四氢叶酸还原酶（MTHFR）基因C677T多态与中国人肝细胞癌（Hcc）遗传易感性的关系。方法采用聚合酶链反应一限制性片段长度多态性（PCR—RFLP）方法，检测508例Hcc与543例对照的MTHFR C677T基因型分布及其差异。结果HCc和对照两组人群的MTHFR C677T基因型分布差异无统计学意义。但与C等位基因携带者（C／C和C／T基因型）相比，T／T基因型携带者患HCC的风险增加0．66倍（95％可信区间为1．08～2．54，P〈0．05）。性别因素分层分析结果显示：T／T基因型女性携带者其HCC的风险是C等位基因女性携带者的2．64倍（95％可信区间为1．19～5．88，P〈0．05）；而男性T／T基因型与C等位基因携带者其HCC的风险差异无统计学意义。结论MTHFR基因C677T多态可能是中国女性患HCC的一个遗传易感因素，而男性HCC发病风险与该多态无明显关系。     

转化生长因子β1启动子区C-509T位点基因多态性与肝纤维化关系

目的:建立多聚酶链式反应-限制性片段长度多态分析(PCR-RFLP)法检测转化生长因子β1(TGF-β1)启动子区C-509T位点的变异并探讨其在肝纤维化中的作用．方法:根据TGF-β1启动子区基因设计引物, 在C-509T位设计Bsu36 I酶切位点,根据PCR 产物酶切结果判断该位点为C或T．观察对象为慢性乙型肝炎患者50例,乙型肝炎后肝硬化患者46例．结果:测序显示本文两株纯合子与TGF-β1启动子区序列同源性在99％以上,并在C-509T 位点出现预期变异:乙型肝炎和乙型肝炎后肝硬化两组都是以CT基因型为主,但是肝硬化组CC基因型(28.3％)高于TT基因型(19．6％), 而肝炎组TT基因型(22％)高于CC基因型(4％), 几组之间有显著性差异(P<0．01)．结论:本文建立的方法可用于TGF-β1启动子区C-509T住点基因多态性的检测,该位点CC 基因型可能与肝纤维化有关．     

Transforming growth factor-beta gene polymorphism in sarcoidosis and tuberculosis patients.

SETTING: Transforming growth factor-beta (TGF-beta) plays an important role in many diseases, influencing as it does such processes as immune responses, fibrosing processes, and angiogenesis. Recently, polymorphisms have been described for TGF-beta that are associated with the risk of several diseases. In this study, we investigated whether TGF-beta 1 polymorphism has an effect on sarcoidosis and tuberculosis. OBJECTIVE: TGF-beta 1 Codon 10 T869C polymorphism was investigated in 110 healthy control subjects, 104 sarcoidosis patients, and 101 tuberculosis patients. DESIGN: The TGF-beta genotype was determined using polymerase chain reaction restriction fragment length polymorphism. RESULTS: We found no significant differences in TGF-beta genotypes between sarcoidosis patients and healthy controls or tuberculosis patients and controls. The long axis of the tuberculin skin test was larger in the CC type compared with the CT type. However, there was no association between the TGF-beta genotype and the roentgenographic stage, the disappearance of shadows, or organ involvement in sarcoidosis, nor any association between genotype, the extent or type of roentgenographic shadow, or detected volume of tubercle bacilli in tuberculosis. CONCLUSION: From the results, we believe that TGF-beta polymorphisms on the whole do not have a strong influence on disease onset or clinical progression in sarcoidosis and tuberculosis, although this polymorphism might have an effect on the immune response in a tuberculosis host.     

Transforming growth factor—β1in invasion and metastasis in colorectal cancer

AIM：To investigate the role of TGFβ1 in invasion and metastasis in colorectal cancer by analysing TGFβ1 correlated wity depth of tumor invasion,stage and metastasis.METHODS:Serum TGFβ1levels were determined in50patients with colorectal cancer and 30healthy volunteers using a TGFβ1 enzyme-linked immunosorbent assay.TGFβ1 expression in primary and lymph node metastatic lesions were detected in 98cases of colorectal cancer by immunohistochemical staining and in situ hybridization.RESULTS:Serum levels of TGFβ1 in patients with colorectal cancer(40&#177;18μg&#183;L^-1)were significantly higher than those in the healthy control group(19&#177;8μg&#183;L^-1),P&lt;0.05.Elevated levels of serum TGFβ1were found in 60%of patients with colorectal cancer when the mean+2s was used as the upper limit of the normal range(35.1μg&#183;L^-1).Increases in serum TGFβ1 levels were significantly asociated with Dukei‘s stage(P&lt;0.05),but there was no significant difference between,Duki‘s stage Bpatients and Dukei‘s stage Cpatients.In the cytoplasm of cancer cells,TGFβ1 was immunostained in37.8%(37/98)of colorectal cancer,and this expression was confirmed by in situ hybridization,Among35cases of colorectal cancer with lymph node metastatic lesions,TGFβ1 positive staining was found in18(51.4%)cases of primary tumor,and 25(71.4%)cases with lymph node metastatic lesions,respectively,Of17cases with no staining in the primary lesion.7(41.2%)casesshowed TGFβ1 staining in the metastatic lesion.Serum TGFβ1 levels and TGFβ1 expression in colorectal cancer tissues were correlated significantly with depth of tumor invasion,stage and metastasis,Patients in stage C-D,T3-T4and with metastasis had significantly higher TGFβ1 levels than patients in stage A-B,T1-T2and without metastasis(P&lt;0.05).CONCLUSION:These results suggest that transforming growth factor-β1 is closely related to the invasion and metastasis of colorectal cancer.It increased the invasive and metastatic potential of tumor by altering a tumor microenvironment.TGFβ1 may be used as a possible biomarke.     

Transforming growth factor-beta1 to the bone

TGF-beta1 is a ubiquitous growth factor that is implicated in the control of proliferation, migration, differentiation, and survival of many different cell types. It influences such diverse processes as embryogenesis, angiogenesis, inflammation, and wound healing. In skeletal tissue, TGF-beta1 plays a major role in development and maintenance, affecting both cartilage and bone metabolism, the latter being the subject of this review. Because it affects both cells of the osteoblast and osteoclast lineage, TGF-beta1 is one of the most important factors in the bone environment, helping to retain the balance between the dynamic processes of bone resorption and bone formation. Many seemingly contradictory reports have been published on the exact functioning of TGF-beta1 in the bone milieu. This review provides an overall picture of the bone-specific actions of TGF-beta1 and reconciles experimental discrepancies that have been reported for this multifunctional cytokine.