谷胱甘肽S转移酶M1、T1和P1基因多态与肝癌易感性研究

目的 探讨谷胱甘肽S转移酶M1、T1和P1基因多态与肝癌的关系.方法 应用PCR技术对84例肝癌患者和144例健康对照的谷胱甘肽S转移酶M1、T1和P1基因多态进行检测.结果 病例组GSTM1和GSTT1空白基因型频率分别为66.67%和40.48%,对照组则分别为47.92%和25.00%,两组差别均有统计学意义(P<0.05);病例组GST13种基因型频率分别为64.29%,33.33%和2.38%,对照组分别为61.80%,34.03%和4.17%,两组差别无统计学意义.平衡性别因素后其比值比分别为2.20,1.93和0.94.同时携带GSTM1空白基因型和GSTT1空白基因型的个体患肝癌的危险性显着增加.结论 GSTM1和GSTT1基因是筛检肝癌高危人群的有用指标.     

谷胱甘肽硫转移酶M1和T1基因多态性与噪声性听力损失易感性的关系研究

目的探讨谷胱甘肽硫转移酶M1和T1(GSTM1和GSTT1)的基因多态性与噪声性听力损失易感性之间的关系。方法采用横断面流行病学研究方法,对194名噪声暴露作业工人进行调查和听力测试,按听力学评价的结果将其分为听力损失组和听力正常组。用多重PCR方法检测其GSTM1和GSTT1的存在空白基因多态性。结果GSTM1和GSTT1的存在空白基因型分布在93名噪声性听力损失与101名听力正常工人之间差异无显著性(P>0.05)。采用多元Logistic回归分析对两组间年龄、性别、吸烟状况、爆震史和累积噪声暴露量等因素进行校正后,发现GSTT1空白基因型组与GSTT1存在基因型组相比噪声性听力损失的危险度显著性升高(P<0.05),调整OR值为1.952(95%可信区间为1.017～3.746);GSTM1存在与空白基因型之间发生噪声性听力损失的相对危险度差异无显著性(P>0.05)。结论谷胱甘肽硫转移酶T1基因多态性可能在噪声性听力损失的发病过程中起一定作用,携带GSTT1空白基因型的个体对噪声性听力损失的易感性升高。     

有机氯农药及谷胱甘肽转移酶M1基因多态性与乳腺癌关系的研究

目的 研究血清中有机氯农药水平及谷胱甘肽转移酶M1(GSTM1)基冈多态性对女性乳腺癌患病风险的交互作用.方法 自2006年9月至2007年10月,在唐山市5所二甲以上医院收集经病理学确诊的乳腺癌患者70例.选取病例所在医院同期住院的女性患者,年龄相差不超过2岁,按相近居住地Ⅸ进行1:1配比作为对照.采用气相色谱-电子捕获(GC-ECD)方法检测血清中有机氯农药[滴滴涕(DDT)包括4种同分异构体:P,P'DDE、P,P'DDT、o,p'DDT、P,P'-DDD;六六六(HCH)包括4种同分异构体:α-HCH、β-HCH、γ-HCH、δ-HCH]残留水平,采用聚合酶链反应(PCR)检测GSTMl基因多态性,根据交互作用系数(γ)判断交互作用存在与否以及不同的基因.环境作用类型.结果 GSTM1基因多态性与DDT及HCH间存在一定的交互作用,交互作用系数分别为1.237、1.379,交互作用分别表现为次相乘模型和超相乘模型.结论 乳腺癌的发生是环境和遗传因素综合作用的结果.GSTM1基因多态性与环境危险因素DDT、HCH的暴露在乳腺癌发生中存在一定的交互作用.

Abstract：

Objective To study the potential effect of gene-environment interaction between glutathione S-transferase M1 (GSTM1) and serum organochlorines residues on the risk of breast cancer in women, in China. Methods Seventy newly pathologically diagnosed female patients with breast cancer from September 2006 to October 2007 were selected as the cases from five large hospitals in Tangshan. The controls were identified at the same hospital as cases. 1:1 matched case-control study. Between the cases and controls, the difference of age was not over two years and the residence was similar. The organochlorine residues levels in the serum were measured by gas chromatography (GC). Genotypes of GSTM1 polymorphisms were analyzed by multiplex allele-specific polymerase chain reaction (PCR). Interaction indexes (γ) were calculated to determine the type of gene-environment interaction. Results After confounding factors adjusted, the result showed that interaction existed in genetic polymorphisms of GSTM1 and DDT, HCH residues, and interaction indexes (γ) value were 1.237 and 1.379. Conclusion GSTM1 genetic polymorphisms and DDT, HCH may present an interaction in the development of breast cancer.     

济南市汉族育龄女性谷胱甘肽硫转移酶基因多态性分析

目的 了解山东省济南市汉族育龄女性谷胱甘肽硫转移酶M1(GSTM1)、T1 (GSTT1)及P1(GSTP1)基因多态性分布特征.方法 选择在济南市第二妇幼保健院进行围孕期保健的344名汉族健康女性为研究对象,采集口腔黏膜上皮脱落细胞提取基因组DNA,使用荧光定量PCR方法检测GSTM1、GSTT1及GSTTP1基因多...     

谷胱甘肽转移酶M1基因多态性与大肠癌发生关系的多水平Meta回归分析

目的探讨谷胱甘肽转移酶（GST）M1基因多态性与大肠癌发生的关系及其影响因素。方法采用多水平Meta回归分析方法进行合并效应值估计和异质性相关因素的研究。结果GSTM1基因多态性与大肠癌发生有关（合并OR值为1．17，95％CI：1．08～1．26），种族类别、人群GSTM1基因基线缺失率等为研究间异质性的相关因素（P〈0．05）；分层回归中，亚洲人、高加索人及低基线缺失水平人群（50％以下）中的GSTM1基因缺失型是大肠癌发生的危险因素（合并OR值分别为1．14、1．25、1．29），结果具有统计学意义（P〈0．05）。结论GSTM1纯合缺失型是大肠癌发生的危险因素，并与人群的GSTM1基线缺失率和种族类别有关。     

谷胱甘肽转移酶M1基因缺失与苯白血病的相关性分析

目的 探讨苯接触工人谷胱甘肽转移酶M1（GSTμ）基因缺失与苯白血病发病的相关性。方法 采用1：1配比的病例－对照研究和多因素条件Logistic回归分析。结果 GSTμ基因缺失者患苯白血病的危险性为GSTμ基因携带者的3．6倍，提示GSTμ基因缺失是苯白血病发病的危险因素。单因素条件Logistic回归分析显示，作用显著的因素依次是GSTμ基因缺失、GSTμ亚型酶活力、接苯工龄、GST总酶活力、吸烟总量和车间空气中苯的平均浓度。经多因素条件Logistic回归分析后，按相对危险度（OR）大小排列，依次是GSTμ基因缺失、接苯工龄和GSTμ亚型酶活力。结论 GSTμ基因缺失在苯白血病的发生过程中起重要作用，可作为探讨苯白血病人群易感性和发现高危人群的效应标志物。     

谷胱甘肽-S-转移酶M1基因多态与食管癌的Meta分析

目的 对谷胱甘肽-S-转移酶M1(GSTM1)基因多态与食管癌的关联性进行Meta分析。方法 以食管癌组与对照组人群基因型分布的OR值为效应指标,各资料间进行一致性检验,以确定采用固定或随机效应模型进行合并分析。发表偏倚评估用漏斗图法进行。结果 共收集国内外相关资料11篇,积累病例1190例,对照1964名,合并OR值为1.197(95％CI:0.846～1.692)。对其中5篇资料按吸烟与否分层,吸烟组合并OR值为1.523(95％CI:1.099～2.109);不吸烟组合并OR值为0.933(95％CI:0.469～1.692)。结论 GSTM1基因多态与食管癌的易感性无关,但携带GSTM1空白基因型的吸烟者患食管癌的危险性可能会增加。     

谷胱甘肽S一转移酶M1、T1基因多态性与抗结核药物所致肝损害易感性的Meta分析

结核病目前仍然是严重危害人类健康的公共卫生问题.研究发现,WHO推荐的标准短程化疗方案主要使用的三种一线药物异烟肼、利福平、吡嗪酰胺,均能引起不同程度、不同频度的不良反应,其中最主要的不良反应是肝损害.     

谷胱甘肽S-转移酶M1基因型与石棉作业工人血液脂质过氧化水平的关系

目的　探讨谷胱甘肽S 转移酶M1(GSTM1)基因型与接触石棉的工人血液发生脂质过氧化的关系。方法　选择 94名石棉作业工人及 5 1名对照工人作为研究对象 ,通过问卷调查收集每个研究对象的一般情况、职业史等。同时测定血浆丙二醛 (MDA)的含量 ,分析淋巴细胞DNA中GSTM1的基因型。结果　石棉作业工人血浆MDA含量为 (0 .2 83± 0 .0 5 4)nmol/L ,明显高于对照组工人 [(0 .16 3± 0 .0 5 3)nmol/L],差异有显著性 (P <0 .0 1) ,但MDA含量与工龄和累积石棉接触剂量之间的相关关系不明显 ;对照组工人携带GSTM1- /-者血浆中的MDA含量 [(0 .190± 0 .0 34 )nmol/L]明显高于携带GSTM1+/+者[(0 .138± 0 .0 5 5 )nmo/L],差异有显著性 (P <0 .0 1) ,而石棉作业工人组虽也有类似趋势 ,但无统计学差异 (P >0 .0 5 ) ;对于石棉作业工人来说 ,在工龄相同或累积石棉接触剂量相同时 ,携带GSTM1- /-者的血浆MDA含量均高于携带GSTM1+/+者 ,但差异均无显著性 (P >0 .0 5 )。结论　接触石棉和GSTM1- /-基因型均与作业工人机体内脂质过氧化有关 ,但石棉的作用可能大于GSTM1基因型的作用。     

谷胱甘肽硫转移酶T1基因拷贝数多态性与铅毒性症状关系

目的探讨铅作业人群谷胱甘肽硫转移酶T1(GSTT1)基因拷贝数多态性与铅引起的临床症状的关系。方法选择广州市某蓄电池行业257名铅作业工人按铅接触水平分为高剂量组和低剂量组,采用统一调查表进行职业健康问卷调查;采用石墨炉原子吸收光谱法测定现场空气铅及工人血铅、尿铅水平;提取铅作业工人周围血DNA,采用实时荧光定量聚合酶链式反应(PCR)法和比较循环阈值(ΔCt)法检测GSTT1基因拷贝数,分析不同铅尘作业环境下作业人员GSTT1基因拷贝数多态性与血铅、尿铅和临床症状的关系。结果铅作业工人GSTT1基因拷贝数与铅毒性相关的临床症状有关,在高剂量组拷贝数小于2的研究对象临床症状发生率是拷贝数为2的3.1倍[比值比(OR)=3.1,95%可信区间(CI)=1.0～9.6,P=0.046],低剂量组拷贝数小于2的研究对象临床症状发生率是拷贝数为2的8.4倍(OR=8.4,95%CI=2.4～29.2,P≤0.001),GSTT1基因拷贝数与血铅、尿铅水平的关系尚未发现有统计学意义。结论GSTT1基因拷贝数多态性与铅毒性相关临床症状有关,拷贝数小于2的GSTT1基因可能是铅中毒易感基因型。     

谷胱甘肽转硫酶M1,T1基因型与胃癌易感性的关系

目的　探讨谷胱甘肽转硫酶Ｍ１（ＧＳＴＭ１）、Ｔ１（ＧＳＴＴ１）基因型与胃癌危险性的关系。方法　采用病例对照分子流行病学研究方法和聚合酶链反应技术, 检测９５ 例原发性胃癌病例和９４ 例对照者ＧＳＴＭ１ 和ＧＳＴＴ１ 基因型。结果　ＧＳＴＭ１ 基因缺失［ＧＳＴＭ１（－ ）］ 频率在病例组和对照组分别是６３－１６％ 和４５．７４％ ,差异有显著性（χ２ ＝５ ．７５,Ｐ＝ ０．０１６ ５） ,ＧＳＴＭ１ 基因缺失与胃癌易感性有关（ＯＲ＝ ２．０３,９５％ 可信区间＝１．０９～３．８０ ）。携带ＧＳＴＭ１（ －） 和ＧＳＴＴ１（＋ ）基因型者发生胃癌的危险性显著高于ＧＳＴＭ１（ ＋） 和ＧＳＴＴ１（ －） 基因型携带者,比值比ＯＲ＝２．９１,９５％ 可信区间＝１．０９～７．８９。ＧＳＴＭ１ 基因缺失同时暴露于吸烟者患胃癌的危险性显著增高（ ＯＲ＝ ８．０６ ,９５％ 可信区间＝ ２．８３ ～２３．６７） 。结论　ＧＳＴＭ１ 基因缺失型可增加胃癌发生的危险性。     

MPO和GSTM1、GSTT1基因多态性与儿童急性白血病易感性分析

目的 探讨髓过氧化物酶（myeloperoxidase,MPO）和谷胱甘肽S-转移酶（glutathione S-transferase,GST） M1、T1基因多态性及其交互作用与儿童急性白血病易感性的关系。方法 155名广东籍儿童急性白血病患者纳入病例组,155健康体检者为对照组。采用巢式聚合酶链式反应检测MPO （G-463A）,GSTT1,GSTM1基因型。采用（口恶）²检验比较各基因型频率在病例组与对照组之间的差异,用OR及95%CI值表示各基因型发生急性白血病的危险度。结果 携带MPO-463位点A突变基因型（GA/AA）可能降低儿童急性白血病发病危险（OR=0.591,95%CI：0.356~0.981,P=0.041）;同时携带GSTT1 null基因和GSTM1 null基因的个体发生发生急性白血病的危险性是同时携带GSTT1 non-null基因和GSTM1non-null基因个体的2.991倍（95%CI：1.578~5.673）;同时携带MPO野生型（GG）基因及GSTT1 null基因和GSTM1 null基因进一步增加发病危险（OR=3.484,95%CI：1.626~7.466,P=0.041）。结论 同时携带MPO野生型（GG）及GSTT1 null基因和GSTM1 null基因的个体发生急性白血病的风险增大,可考虑作为儿童急性白血病易感性的重要生物标志物。     

Associations of plasma aflatoxin B1-albumin adduct level with plasma selenium level and genetic polymorphisms of glutathione S-transferase M1 and T1

Mortality from hepatocellular carcinoma (HCC) is extraordinarily high in Matzu, an island off the coast of Southeastern China. To investigate factors associated with plasma aflatoxin B1 (AFB1)-albumin adduct level, we studied 304 healthy adult residents from Matzu. AFB1-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen status by enzyme immunoassay, genotypes of glutathione S-transferase (GST) M1 and T1 by polymerase chain reaction, plasma selenium by atomic absorption spectrometry, and plasma retinol, alpha-tocopherol, alpha-carotene, and beta-carotene levels by high-performance liquid chromatography. Men had higher AFB1-albumin adduct levels than women. GSTM1-nonnull and GSTT1-null genotypes and low plasma selenium level were significantly associated with an increased level of AFB1-albumin adducts among men, whereas age was significantly correlated with adduct level among women. High intake of fermented beans was associated with an increased adduct level among men and women. The inverse associations between plasma selenium level and AFB1-albumin adducts were statistically significant among those with null genotypes of GSTM1 and GSTT1, but not among the nonnull genotypes. This study provides insight into the dietary and genetic factors influencing AFB1-albumin adduct formation in an isolated population with high liver cancer mortality.     

Variability in aflatoxin-albumin adduct levels and effects of hepatitis B and C virus infection and glutathione S-transferase M1 and T1 genotype

Exposure to aflatoxin B1 (AFB1), an important cofactor in the etiology of hepatocellular carcinoma in Taiwan, is influenced by dietary and other factors. The present study examined the intraindividual variability in AFB1-albumin adducts, the most reliable long-term biomarker of AFB1 exposure, and whether the baseline or follow-up adduct levels and the intraindividual variability in adduct levels are modified by endogenous and environmental factors. The study measured AFB1-albumin adduct levels among 264 healthy male residents of three townships (Hu-Hsi, Ma-Kung, and Pai-Hsa) of Penghu Islets, Taiwan, at two different time points with a median interval of 1.68 years (range 1.00-3.17 years). There was a generalized reduction in the adduct levels, with the median values being 22.1 pmol/mg (range 5.0-355.8 pmol/mg) at time 1 and 14.3 pmol/mg (range 5.0-205.2 pmol/mg) at time 2. This intraindividual variability in adduct levels was inversely associated with the age of subjects and the time interval between the two blood draws. The variability in adduct levels was lower among subjects in Hu-Hsi and Pai-Hsa townships as compared to those in Ma-Kung. No significant association was observed for the intraindividual variability in AFB1-albumin adducts with regard to the season when blood was drawn. There was also no significant association between intraindividual variability and hepatitis B surface antigen, anti-hepatitis C virus (anti-HCV), glutathione S-transferase (GST) M1, or GSTT1 status. In conclusion, we found substantial intraindividual variability in the AFB1 exposure (as determined by AFB1-albumin adducts) in Taiwan, which was probably more likely related to dietary or other environmental influences rather than to endogenous factors (e.g., hepatitis B/C viral infection or GST M1/T1 genetic status).     

The role of polymorphisms of glutathione S-transferases GSTM1, M3, P1, T1 and A1 in susceptibility to alcoholic liver disease

AIMS AND METHODS: Oxidant stress is proposed to be an important pathogenic factor in liver damage related to alcohol. The glutathione S-transferases (GSTs) are a group of polymorphic enzymes that are important in protection against oxidant stress. As there is evidence for genetic susceptibility to alcohol-related liver disease we have compared the frequency of polymorphisms of GSTM1, M3, P1, T1 and A1 by polymerase chain reaction (PCR) on leucocyte DNA in patients from North Staffordshire, Birmingham and Liverpool with alcohol-related chronic liver disease heavy drinking and normal local controls. RESULTS: There were no significant differences in GSTM1, GSTM3 or GSTP1 genotype frequencies among patients, drinking and non-drinking controls from the three centres. There was a significant increase in the GSTT1 null Liverpool alcoholic liver disease (ALD) patients compared with corresponding non-drinking controls (26.3 and 14.6%, respectively; P = 0.044, odds ratio (OR) = 2.1, 95% CI = 1.1-4.7) though this was not repeated in the Birmingham and North Staffordshire cohorts. For GSTA1, the -69 CC genotype was associated with increased risk of ALD in the Liverpool group, but a reduced risk in the North Staffordshire group. CONCLUSIONS: We have failed to demonstrate within the limitation of a case-control study a reproducible significant association of GST polymorphisms with susceptibility to ALD but there are suggestions that GSTA1 and GSTT1 warrant further study.     

CYP1A1和CYP1B1基因多态性与RPL易感性

目的 探讨CYP1A1、CYP1B1基因多态性与复发性流产(RPL)遗传易感性关系,为预防和治疗该病提供新靶点。方法 本研究采用等位基因特异性PCR(As-PCR)和聚合酶链反应-限制性片断长度多态性(PCR-RFLP)方法,针对CYP1A1基因MspΙ酶切位点和CYP1B1 L432V多态位点,检测81例患有原因不明RPL病例组和98名有生育史健康女性对照组之间差异。结果 RPL组和对照组CYP1A1 MspΙ位点3种基因型m1/m1、m1/m2、m2/m2分布频率差异无统计学意义(χ²=0.335,P>0.05);CYP1B1 L432V多态位点3种基因型C/C、C/G、G/G在病例组和对照组分布差异有统计学意义(χ²=7.467,P<0.05);2组间C、G等位基因分布差异有统计学意义(χ²=9.129,P=0.003);G/G、C/G基因型与C/C基因型比较,RPL危险度分别提高2.620、1.954倍;等位基因G使RPL危险性增加2.038倍。结论 CYP1B1 L432V突变基因型增加RPL发病风险,尚不能认为CYP1A1基因MspI位点多态性与RPL易感性有关。     

IL-4基因多态性与HBV遗传易感性的研究

目的 探讨白介素4(interleukin-4,IL-4)基因的单核苷酸多态性(single nucleotide polymorphisms,SNPs)与皖汉族人群乙型肝炎病毒(hepatitis B virus,HBV)遗传易感性的关系.方法 采用病例对照研究,501位慢性乙型肝炎(chronic hepatitis B,CHB)患者和301位急性自限性HBV感染者分别组成病例组和对照组;采用多重单碱基延伸SNP分型技术(Multiplex SNaPshot),检测两组人群的IL-4基因rs2227284G/T、rs2243283C/G和rs2243288A/G 3个标签SNPs位点的单核苷酸多态性,分析两组间的等位基因频率、单体型频率、基因型是否存在统计学差异.结果 IL-4基因3个多态位点的基因型频率在两组间差异均无统计学意义(均有P＞0.05);IL-4基因3个态位点最小等位基因及其频率在两组间差异均无统计学意义(均有P ＞0.05);4个单体型GCA、TCA、TCG及TGG两组间差异均无统计学意义(均有P＞0.05).结论 皖汉族人群中IL-4基因的3个tagSNPs(rs2227284,rs2243283和rs2243288)位点的基因多态性与HBV感染的基因易感性可能无相关性.     

Plasma carotenoids, glutathione S-transferase M1 and T1 genetic polymorphisms, and risk of hepatocellular carcinoma: independent and interactive effects

This study was conducted to assess the role of carotenoid and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in the development of hepatocellular carcinoma (HCC). A total of 84 incident cases of HCC and 375 matched controls selected from a cohort of 7,342 men (4,841 chronic hepatitis B carriers and 2,501 noncarriers) who were recruited between 1988 and 1992 in Taiwan were studied. Neither GST M1/T1 polymorphisms nor plasma levels of various carotenoids were independently associated with HCC, but they modulated smoking- and/or drinking-related HCC risk. Cumulative exposure to tobacco smoke significantly increased HCC risk in a dose-dependent manner among subjects with low plasma beta-carotene levels (p for trend = 0.047) but not among those with high levels. A statistically significant effect of habitual alcohol drinking on HCC risk was observed only for those with low plasma levels of beta-carotene, alpha-carotene, or lycopene and for GST M1 null subjects. There was evidence suggesting an interaction between the GST M1/T1 genotype and certain carotenoids in HCC associated with smoking and drinking. The strongest effect of smoking and drinking was noted among GST M1 null subjects with low plasma levels of beta-carotene (smoking: adjusted odds ratio (OR) = 3.54, 95% confidence interval (CI) 1.06-11.83; drinking: OR = 8.28, 95% CI 2.40-28.61).