GSTM1及GSTT1基因多态性与宫颈癌关系的研究

目的：探讨GSTM1及GSTT1基因多态性与宫颈癌发生的关系.方法：采用以医院为基础的病例对照及分子流行病学研究方法,应用多重PCR技术检测125例宫颈癌病例和125例子宫肌瘤对照的GSTM1和GSTT1基因型.结果：病例组GSTM1基因纯合缺失率为58.4%,显著高于对照组43.2%（x^2=5.777,P=0.016）;GSTT1基因纯合缺失率在病例组和对照组分别为53.6%和44.0%,差别无统计学意义（x^2=2.305,P=0.129）;GSTM1和GSTT1联合缺失者患宫颈癌的危险性是两基因同时存在者的2.588倍（95%CI=1.285～5.212）.结论：GSTM1基因纯合缺失或GSTM1、GSTT1联合缺失可能与宫颈癌的发生有关.     

芳香烃受体基因G1661A多态性与焦炉工尿中1-羟基芘水平的关系

目的 研究芳香烃受体(AhR)基因G1661A多态性与焦炉工尿中1-羟基芘水平的关系.方法 选取214名男性焦炉工和81名无多环芳烃职业性接触的男性工人为研究对象,收集研究对象的年龄、吸烟和饮酒、职业暴露史等信息,应用等位基因特异性扩增(ASA)方法检测AhR基因型,使用高效液相色谱-荧光检测器法测定工人尿中1-羟基芘的水平.结果 G/G、G/A和A/A3种基因型在接触组中的分布频率分别为52.8%(113/214)、27.6%(59/214)和19.6%(42/214),在对照组的分布频率分别为67.9%(55/81)、19.8%(16/81)和12.3%(10/81),2组基因型分布频率比较,差异无统计学意义(P》0.05);接触组G、A等位基因频率分别为66.6%(285/428)和33.4%(143/428),对照组分别为77.8%(126/162)和22.2%(36/162),2组等位基因频率比较,差异无统计学意义(P》0.05).经过广义线性模型对工人的作业工龄和外暴露等级校正后,用协方差分析方法分析发现,A/A、G/A、G/G 3种基因型者对数转换后尿中1-羟基芘的水平分别为(3.62±0.12)、(3.43±0.12)和(3.44±0.08)μmol/mol Cr,携带G、A等位基因的个体对数转换后尿中1-羟基芘的水平分别为(3.24±0.09)和(3.43±0.10)μmol/mol Cr,不同基因型及等位基因型的焦炉工尿中1-羟基比水平比较,差异无统计学意义(P》0.05).结论 焦炉工AhR基因G1661A多态性对尿中1-羟基芘的水平无明显影响.     

焦炉工血清GST活力与尿1-羟基芘和GSTM1、GSTT1基因多态的关系

目的研究血清谷胱甘肽硫转移酶(GST)能否作为焦炉工人多环芳烃的暴露评价指标,同时探讨GSTM1、GSTI1基因多态性与血清GST活力的关系.方法选择某焦化厂39名男性焦炉工人和44名男性对照工人,采用统一的调查表调查一般情况.采集静脉血分析血清GST活力和GSTM1、GSTT1基因型,采集尿样分析尿1-羟基芘(1-OHP)浓度.血清GST活力用试剂盒检测;尿1-羟基芘(1-OHP)浓度作为多环芳烃内暴露剂量,用碱水解-高效液相色谱方法测定;GSTM1和GSTT1基因多态性分析采用PCR方法.结果焦炉工人尿1-OHP浓度(中位数为5.60μmol/mol肌酐)和血清GST活力(中位数25.75 U/ml)分别高于对照组(尿1-OHP浓度:中位数1.32 μmol/mol肌酐,血清GST活力:14.54 U/ml),差异均有统计学意义(均P＜0.001).GSTM1(-/-)和GSTT1(-/-)型工人的血清GST活力分别与GSTM1(-/ , / )和GSTT1(-/ , / )型工人的血清GST活力相比,差异均无统计学意义(均P＞0.05).广义线性回归分析显示,尿1-OHP对血清GST的影响具有统计学意义(P＜0.01).血清GST活力和尿1-OHP浓度存在统计学正相关(r=0.357,P＜0.001,n=83).结论焦炉工人血清GST有可能作为多环芳烃暴露评价的参数;未见GSTM1和GSTT1基因缺失对血清GST活力的影响.     

微粒体环氧化物水化酶基因多态性对焦炉工尿中1-羟基芘水平的影响

目的　研究外源性化学物代谢酶基因多态性与焦炉工尿中 1 羟基芘水平的关系。方法　分别选取 14 8名焦炉工和 6 9名非职业多环芳烃 (PAHs)暴露人员作为研究对象 ,使用碱水解 -高效液相色谱法测定其尿中 1 羟基芘浓度 ;分析了CYP1A1基因第 7外显子I4 6 2V位点、GSTM1、GSTT1、GSTP1基因I10 5V位点、CYP2E1基因 5’非编码区的Pst1位点和第 6内含子的Dra1位点、NQO1基因P187S位点、NAT2基因Kpn1、BamH1和Taq1位点以及mEH基因H113Y和R139H位点的多态性 ;使用调查表收集个人职业暴露史、年龄、性别、吸烟和饮酒等信息。结果　焦炉工尿中 1 羟基芘水平[(5 .6 1± 1.0 4 ) μmol molCr]高于对照组 [(0 .74± 0 .32 ) μmol molCr],差异有显著性 (P <0 .0 5 )。调整了PAHs外暴露等级和吸烟因素后 ,焦炉工中具有mEH基因 113位点变异纯合子基因型个体尿中1 羟基芘水平高于杂合子和野生型纯合子 (6 .4 1± 1.0 9>6 .2 4± 1.0 9>4 .6 2± 0 .95 μmol molCr) ,且野生型纯合子与变异型纯合子基因型个体间尿中 1 羟基芘水平的差异有显著性 (P <0 .0 5 )。在焦炉工中还发现CYP1A1和mEH基因多态性存在交互作用。结论　mEH基因 113位点的基因多态性可明显影响焦炉工尿中 1 羟基芘水平。     

GSTM1、GSTT1及GSTP1基因多态性与子宫内膜异位症的相关性研究

目的:探讨唐山地区汉族妇女谷胱甘肽S-转移酶超家族成员GSTM1、GSTT1及GSTP1基因多态性与子宫内膜异位症遗传易感性的关系。方法:采用MD-PCR和RFLP-PCR技术检测94例子宫内膜异位症患者和102例对照妇女的GSTM1、GSTT1及GSTP1的基因型。结果:GSTM1、GSTT1、GSTP1各基因型在病例组和对照组中的分布,差异无统计学意义(P>0.05),携带AG基因型个体患病的风险是携带AA基因型个体的1.74倍,GSTP1各等位基因在各组中的分布无统计学差异。结论:未发现GSTM1、GSTT1、GSTP1基因多态性与子宫内膜异位症有关,尚不能认为GSTM1和GSTT1缺失基因型是子宫内膜异位症的易感基因型。     

CYP1A1基因多态性与焦炉工尿中1-羟基芘水平的关系

目的 研究CYPIAl多态性与焦炉工尿中1-羟基芘水平的关系.方法 按照苯并[a]芘(B[a]P)接触水平将223名焦炉工分为炉顶组(76名)、炉侧组(82名)和炉底组(65名),以119名无职业性接触多环芳烃的工人为对照组,采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)CYPIAl基因Mspl位点多态性、等位基凶特异性扩增方法 检测CYPlAl基因1462V位点的多态性.结果 炉顶组、炉侧组和炉底组焦炉工尿中1-羟基芘水平分别为(3.77+0.64)、(3.57+0.49)、(3.26+0.80)μmol/mol Cr,明显高于对照组,差异有统计学意义(PO.05).炉侧组和炉顶组CYPIAl 1462V位点的各基因型尿中1-羟基芘水平均为Ⅱe/Ⅱe<Ⅱe/Val相似文献   

广东省梅州地区客家人群GSTP1和GSTM1基因多态性研究

目的了解谷胱甘肽硫转移酶P1(GSTP1)、M1(GSTM1)基因多态性在广东梅州地区人群中的分布规律.方法采用聚合酶链式反应-限制性酶切片段长度多态性(PCR-RFLP)方法和以β-Globin为内对照的双重PCR法分别检测广东省梅州地区512名健康客家居民GSTP1和GSTM1基因型.结果调查人群GSTP1基因3种基因型GSTP1 A/A、GSTP1A/G、GSTP1 G/G分布频率分别为69.1%,28.2%,2.7%;GSTM1基因缺失型分布频率为62.1%;GSTM1基因在饮酒人群与不饮酒人群中的分布差异有统计学意义(P＜0.05),GSTP1基因在吸烟与不吸烟人群中的分布差异有统计学意义(P＜0.01),吸烟人群中GSTP1 A/A基因型分布频率较低(62.5%),GSTP1 A/G基因型分布频率较低(29.2%),GSTP1 G/G基因型分布频率较高(8.3%).GSTM1基因型分布与高血压家族史有相关性(OR=1.868,95%CI 1.119～3.119).结论 GSTP1基因多态性在广东梅州地区吸烟与不吸烟客家人群中分布有差异,GSTM1在广东梅州地区饮酒与不饮酒客家人群中分布有差异,GSTM1基因型分布与高血压家族史有相关性.     

海南汉族健康人群GSTT1、GSTM1基因多态性分析

目的探讨海南汉族人群谷胱甘肽S转移酶GSTM1基因和GSTT1基因多态性分布情况。方法应用多重PCR扩增方法检测147名汉族健康人群GSTM1基因型和GSTT1基因型。结果147名海南汉族人群中,GSTM1-基因型频率为56.5%(83/147),GSTT1-基因型频率为40.8%(60/147),GSTM1-/GSTT1-基因型频率为25.2%(37/147),2基因在正常人群中分布与年龄、性别无关,且相互独立无关联。结论海南汉族健康人群GSTM1基因和GSTT1基因多态性与不同地区正常人群之间存在一定差异性(P<0.01)。     

GSTT1和GSTM1基因多态性与人体砷甲基化代谢水平关系探讨

目的探讨GSTT1、GSTM1基因多态性与人体砷甲基化代谢水平之间的关系。方法选择某工业性砷污染区的247名成年常住居民为研究对象。采用多重PCR法检测GSTM1和GSTT1基因多态性。离子色谱氢化物发生原子荧光法(IC-HG-AFS)测定尿中无机砷(iAs)、一甲基胂酸(MMA)和二甲基胂酸(DMA)。结果GSTT1缺失基因型人群与GSTT1非缺失基因型人群尿中iAs比例、DMA比例和MMA比例相比较,差异均无统计学意义(P>0.05)。GSTM1缺失基因型人群与GSTM1非缺失基因型人群尿中iAs比例、DMA比例和MMA比例相比较,差异均无统计学意义(P>0.05)。四组不同GSTT1和GSTM1联合基因型人群尿中iAs比例、DMA比例和MMA比例相比较,四组间差异也均无统计学意义(P>0.05)。结论本研究未发现GSTT1、GSTM1基因多态性与砷代谢水平之间存在显著关联。     

GSTT1及GSTM1和CYP2E1基因多态性与二甲基甲酰胺所致肝脏损害的关系

目的 探讨GSTT1、GSTM1和CYP2E1基因多态性与二甲基甲酰胺(DMF)作业人员肝脏损害的关系.方法 以某皮革厂69名肝功能异常的DMF作业人员为病例组,选取与病例组相似岗位、DMF接触水平相近而肝功能正常的125名工人为对照组,应用聚合酶链反应(PCR)、PCR-RFLP方法分别对GSIT1、GSTM1和CYP2E1 PstI位点基因进行分型.结果 病例组和对照组中GSTM1阳性和GSTM1阴性的分布频率分别为59.42%、38.40%和40.58%、61.60%,两组间分布的差异有统计学意义(P=0.005),携带GSTM1阳性基因型个体发生肝功能异常的风险是GSTM1阴性基因型个体的2.34倍(OR=2.34,95%CI:1.29～4.29).而GSTT1和CYP2E1 PstI位点不同基因型在病例组和对照组中没有明显差异.结论 携带GSTM1阳性基因型个体的DMF作业人员发生肝功能异常的风险性可能增加.     

Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesions

OBJECTIVE: We investigated whether primary and secondary arsenic methylation ratios were associated with skin lesions and whether GSTT1, GSTP1, and GSTM1 polymorphisms modify these relationships. METHODS: A case-control study of 600 cases and 600 controls that were frequency matched on age and sex was conducted in Pabna, Bangladesh, in 2001-2002. Individual well water, urine, and blood samples were collected. Water arsenic concentration was determined using inductively coupled plasma mass spectrometry (ICP-MS). Urinary arsenic speciation was determined using high performance liquid chromatography hydride with generator atomic absorption spectrometry and ICP-MS. Genotyping was conducted using multiplex polymerase chain reaction and TaqMan. RESULTS: A 10-fold increase in primary methylation ratio [monomethylarsonic acid (MMA)/(arsenite + arsenate] was associated with a 1.50-fold increased risk of skin lesions (multivariate odds ratio = 1.50; 95% confidence interval, 1.00-2.26). We observed significant interaction on the multiplicative scale between GSTT1 wildtype and secondary methylation ratio [dimethylarsinic acid/MMA; likelihood ratio test (LRT), p = 0.01]. No significant interactions were observed for GSTM1 or GSTP1 or for primary methylation ratios. CONCLUSION: Our findings suggest that increasing primary methylation ratios are associated with an increase in risk of arsenic-related skin lesions. The interaction between GSTT1 wildtype and secondary methylation ratio modifies risk of skin lesions among arsenic-exposed individuals.     

GSTM1, GSTT1, GSTP1, and GSTA1 polymorphisms and urinary isothiocyanate metabolites following broccoli consumption in humans

Isothiocyanates (ITC) are potentially anticarcinogenic phytochemicals formed from the metabolism of glucosinolates and are found in cruciferous vegetables as well as a select number of other foods. ITC are both substrates for and inducers of glutathione S-transferase (GST) phase II metabolizing enzymes involved in carcinogen detoxification as well as effectors of phase I pathways. Previous studies report mixed results on the interaction between cruciferous vegetable intake, GST polymorphisms, and risk of cancer. We conducted a study of 114 healthy human subjects between 18 and 50 y of age to examine the biologic mechanism underlying the associations, specifically, to assess whether GST genotype is associated with urinary ITC metabolites following a known dose of broccoli. After 48 h of abstaining from all sources of glucosinolates, participants provided a blood sample, consumed 1 meal containing 2.5 g broccoli/kg body weight, and collected urine for 24 h. ITC metabolites were measured in the urine using a HPLC cyclocondensation assay. DNA was extracted from blood samples, and GSTM1 deletion, GSTT1 deletion, GSTP1 Ile105Val, and GSTA1*A/*B were genotyped by matrix-assisted laser desorption/ionization time-of-flight. A chi-square test was used to compare high and low ITC excretion levels across genotypes. ITC levels were regressed on genotype, adjusting for gender. There were no substantial differences in ITC levels among genotypes, either individually or in combination. Contrary to our hypothesis, a higher proportion of GSTM1 null individuals had high ITC excretion (62%) compared with the proportion of GSTM1 present with high ITC excretion (39%) (P = 0.03). These results are in agreement with another feeding study, and lend support to the idea of alternative routes of ITC metabolism.     

炼焦职业暴露工人与对照人群尿中1-羟基芘水平比较

目的比较焦炉工和非职业暴露人群尿中1-羟基芘的不同水平,并探讨可能的各种影响因素.方法 2002年上半年,以某焦化厂265名炼焦作业工人和226名非职业接触对照人群为调查对象,职业接触组收集工作班末尿,对照组收集晨尿.根据环境中多环芳烃监测和调查表评价外暴露因素和可能的混杂因素,采用高效液相色谱法测定尿中1-羟基芘含量,比较两组人群尿中1-羟基芘的不同水平,并分析外暴露等级、吸烟、饮酒、年龄和体重指数的可能影响.结果尿中1-羟基芘浓度呈炉顶工〉炉侧工〉炉底工〉对照的趋势,几何均数依次为13.49、6.56、1.38和0.35 μmol/mol肌酐,差异有统计学意义;各组人群尿中1-羟基芘浓度超标率分别依次为94.81%、84.73%、35.09%和0.88%,差异有统计学意义.对照人群中≥20支/d吸烟组的尿中1-羟基芘水平明显高于不吸烟组,修正几何均数分别为0.47和0.31 μmol/mol肌酐,差异有统计学意义;对照人群中饮酒组的尿中1-羟基芘水平明显低于不饮酒组,修正几何均数分别为0.33和0.47 μmol/mol肌酐,差异有统计学意义.结论焦炉工尿中1-羟基芘水平较高,以炉侧工和炉顶工最为明显,非职业暴露人群尿中1-羟基芘本底水平与吸烟和饮酒因素有关.     

GSTM1和GSTT1基因多态性与噪声性听力损失易感性的关系

目的探讨GSTM1和GSTT1基因多态性与噪声性听力损失易感性的关系。方法采用病例对照研究方法和多重聚合酶链反应(PCR)技术检测听损组123(118)例和对照组123(114)例的GSTM1和GSTT1基因缺失型频率,以2检验检测听损组和对照组基因型频率的差异。结果GSTM1基因在听损组和正常组的缺失率分别为69.1%和56.1%,差异具有统计学意义(P<0.05)。GSTM1(-)基因型携带者发生噪声性听力损失的危险性是携带GSTM1( )基因型者的1.75倍。GSTT1基因在听损组和正常组的缺失率为50.8%和57.9%,差异没有统计学意义(P>0.05)。联合分析表明,携带GSTM1(-)和GSTT1(-)基因型者发生噪声性听力损失的危险性虽稍高于携带GSTM1( )和GSTT1( )基因型者(OR=1.11,2=0.16,P>0.05),但差异无统计学意义,由此认为GSTM1和GSTT1基因之间可能不存在联合作用。结论GSTM1基因缺失可能是发生噪声性听力损失的易感因素之一。     

XRCC1基因多态与肺癌易感性的关系

目的 探讨DNA修复基因XRCC1多态对肺癌发生易感性的影响.方法 采用病例对照研究的方法选择209例肺癌患者为病例组,256例健康检查者为对照组,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测XRCC1基因194、280和399位点的多态性.结果 病例组与对照组XRCC 1-194位点Trp/Trp变异基因型分布频率分别为19.1％、10.9％,两组比较,差异有统计学意义(P＜0.05).该变异基因型携带者发生肺癌的危险度是野生型携带者的2.215倍(95％CI为1.276～3.845).病例组与对照组XRCC1-280位点Hi,His变异基因型分布频率分别为6.7％、4.3％,两组比较,差异有统计学意义(P＜0.05).该变异基因型携带者发生肺癌的危险度是野生型携带者的2.460倍(95％CI为1.141～5.304).病例组与对照组XRCC 1-399位点Gln/Gln基因型分布频率分别为10.0％、9.0％,两组比较,差异无统计学意义(P＞0.05).XRCC1-194、XRCC 1-280多态基因位点与吸烟在肺癌发生中均存在交互作用,携带XRCC1-194 Arg/Trp+Trp+Trp基因型和XRCC 1-280 His/His+Arg/His基因型的吸烟人群患肺癌的危险度分别为4.889(95％CI为2.828～8.452)和6.281(95％CI为3.572～11.046),明显高于携带野生基因型的非吸烟者.结论 携带XRCC1-194 Trp/Trp和XRCC 1-280 His/His突变等位基因及其与吸烟的交互作用使肺癌发生的风险增加,XRCC1基因多态与吸烟在肺癌的发生过程中起一定作用.     

Study on the relationship between GSTM1, GSTT1 gene polymorphisms and arsenic methylation level

OBJECTIVE: To investigate the relationship between genetic polymorphisms of GSTT1, GSTM1 and arsenic methylation level. METHODS: 247 residents in an industrial arsenic polluted village were randomly selected as subjects. The genetic polymorphisms of GSTM1 and GSTT1 were detected by multiple PCR method. Urinary inorganic arsenic (iAs), monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA) concentrations were determined by ion chromatogram combined with HG-AFS. RESULTS: No significant differences in the relative proportion of urinary iAs, MMA and DMA were observed between the individuals with GSTT1 positive genotype and the individuals with GSTT1 null genotype. No significant differences in the relative proportion of urinary iAs, MMA and DMA were observed between the individuals with GSTM1 positive genotype and the individuals with GSTM1 null genotype. And no significant differences in the relative proportion of urinary iAs, MMA and DMA was observed among the individuals with different GSTM1 and GSTT1 associated genotype. CONCLUSION: The polymorphisms of GSTT1 and GSTM1 were not associated with arsenic metabolism level in the studied population.