脐血中谷胱甘肽s转移酶基因多态性与维汉新生儿低出生体重的关系

目的探讨乌鲁木齐市维吾尔族与汉族新生儿脐带血中谷胱甘肽s转移酶(GST)M1与T1基因多态性与低出生体重的关系。方法采用1∶3病例对照研究方法,收集新生儿脐带血并提取DNA,采用多重等位基因特异聚合酶链反应(PCR)方法分析GSTM1和GSTT1基因多态性。结果GSTM1缺失基因型为60.5%,GSTT1缺失基因型为5%,同时具有GSTM1和GSTT1缺失基因型的频率为3.5%。正常出生体重新生儿脐血中GSTT1基因型缺失的频率与低出生体重儿之间差异有统计学意义(P0.05)。GSTT1基因型缺失的频率在维吾尔族正常与低出生体重新生儿间差异有统计学意义(P0.05)。维吾尔族正常出生体重与低出生体重新生儿间各组合基因型频率构成比分布差异有统计学意义(P0.05)。结论脐血中GSTT1基因型缺失可能会增加新生儿低出生体重的发生,也会增加维吾尔族新生儿低出生体重的发生。而脐血中GSTM1基因型缺失可能不会影响新生儿低出生体重的发生。维吾尔族不同出生体重新生儿间各组合基因型频率构成比分布有差异。因此应全面了解低出生体重发生的原因,从而提高新生儿的出生质量。     

肺癌易感性标记物与肺癌关系的病例对照研究

目的探讨谷胱甘肽转移酶(GST)和细胞色素CYP1A1、CYP2E1多态性与肺癌易感性的关系。方法用病例对照研究方法，收集广东籍新发原发性肺癌病人91例及同期非肺部疾患住院病人91例作对照。采用聚合酶链式反应(PCR)和限制性片段长度多态性(RFLP)技术检测病例和对照的CYP1A1、CYP2E1和GSTM1基因多态性。结果CYP1A1突变型(m2m2)与野生型(m1m1)比较，OR值1．51；CYP2E1C1C1型与C1C2型比较，OR值1．80；C2C2型与C1C2型比较，OR值5．48；GSTM1基因缺失型与正常型比较；OR值1．26。两种基因联合分析结果表明：GSTM，基因缺失并携带CYP1A1m2m2与GSTM1基因正常并携带CYP1A1m1m1者比较，OR值2．29，GSTM1基因缺失并携带CYP2E1C1C1型者与GSTM1基因正常并携带CYP2E1C1C2型者比较，OR值2．13，携带CYP1A1m2m2型以及CYP2E1C1C1型者与携带CYP1A1m1m1型和CYPE1C1C2型者比较，OR值3．00。3种基因联合作用分析结果表明：携带CYP1A1m2m2型以及CYP2E1C1C1型并且GSTM1基因缺失者比携带CYP1A1m1m1型和CYP2E1ClC2型且GSTM1基因正常者提高了患肺癌的危险性，OR值3．97。结论CYP1A1、CYP2E1和GSTM1在单因素分析中末显示出与肺癌风险的联系，2个基因和3种基因的联合作用似乎可以提高患肺癌的危险性，但无统计学意义。提示这3种基因均不是肺癌个体易感性的主效基因，可能是次效基因。     

NQO1、GSTT1和GSTM1基因多态性与慢性苯中毒的遗传易感性

目的探讨NQO1、GSTT1和GSTM1基因多态性与慢性苯中毒遗传易感性之间的关系。方法选择100名慢性苯中毒病例为病例组及90名同期接苯但无苯中毒表现的同工种工人为对照组,应用PCR-RFLP及多重PCR方法判定NQO1、GSTT1和GSTM1基因型。结果携带NQO1C609TT/T基因型(纯合突变型)个体发生苯中毒的危险性是具有C/T基因型(杂合型)和C/C基因型(野生型)个体的2.82倍(95%CI1.42～5.58,P<0.05),是具有C/C基因型(野生型)个体的2.94倍(95%CI1.25～6.90,P<0.05);携带GSTT1缺失(null)基因型个体发生苯中毒的危险性是具GSTT1非缺失(non-null)基因型个体的1.91倍(95%CI1.05～3.45,P<0.05),未发现GSTM1基因型与苯中毒的关系。同时携带NQO1C609TT/T基因型、GSTT1缺失、GSTM1缺失任何两种基因型的个体发生苯中毒的危险性均高于同时携带野生型及非缺失基因型的个体;并且同时携带NQO1C609TT/T基因型、GSTT1缺失与GSTM1缺失个体接苯时发生苯中毒的危险性最高,是NQO1C609TC/T基因型和C/C基因型、GSTT1非缺失型(non-null)与GSTM1非缺失型(non-null)个体的20.41倍(95%CI3.79～111.11,P<0.01)。结论基因之间的交互作用在苯中毒的发生中起重要作用。同时携带NQO1C609TT/T基因型、GSTT1缺失基因型和GSTM1缺失基因型个体发生苯中毒的风险最     

母亲和新生儿GSTM1、GSTT1和细胞色素P_(450)1A1基因多态性与早产易感性关系

目的探讨母亲和新生儿GSTM1、GSTT1基因以及细胞色素P4501A1基因多态性对早产的影响。方法采用病例-对照调查方法,应用多重PCR和限制性内切酶PCR(RFLP-PCR)技术对早产母亲和对照母亲以及早产新生儿和对照新生儿GSTM1、GSTT1基因和CYP1A1基因MSPI位点多态性分别进行检测。结果GSTM1、GSTT1基因和CYP1A1基因MSPI位点多态性在早产母亲和对照母亲组中没有显著性差异(P>0.05);以上基因在早产新生儿和对照新生儿组中也没有显著性差异(P>0.05)。GSTM1与GSTT1联合基因型在母亲和新生儿的病例与对照组中也没有显著性差异(P>0.05);GSTT1缺失型和CYP1A1变异型联合基因在早产母亲组与对照母亲组中有显著性差异(χ2=4.683,P<0.05,OR=2.440)。结论携带GSTT1缺失型基因以及CYP1A1变异型基因的母亲,其发生早产的危险性增大。     

河南省人群五种基因多态性与肺癌易感性的关系

目的探讨河南省人群中外源性化合物代谢酶CYP1A1、GSTM1、GSTT1、mEH和DNA修复酶XRCC1基因多态性与肺癌易感性的关系。方法采用病例-对照研究的方法,选取河南省209例肺癌患者为病例组,256例健康体检者为对照组,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测I相代谢酶基因CYP1A1,II相代谢酶基因GSTM1、GSTT1、mEH及DNA修复酶基因XRCC1的多态基因型。结果河南省人群中GSTM1缺失型,CYP1A1-exon7、mEH-exon3、XRCC1-194及XRCC1-280基因纯和突变型在病例组与对照组中的分布频率差异均有统计学意义(P<0.05),GSTM1基因缺失者与GSTM1基因阳性者相比发生肺癌的危险性升高(ORadj=1.76,95%CI:1.21-2.56,P=0.005);携带CYP1A1-exon7 Ile/val+val/val基因型的个体较携带CYP1A1-exon7 Ile/Ile基因型的个体发生肺癌的危险性升高(ORadj=1.65,95%CI:1.16-2.39,P=0.009);mEH-exon3突变基因型携带者与野生纯合型的个体相比发生肺癌的危险性升高(ORadj=1.77,95%CI:1.18-2.64,P=0.007);携带XRCC1-194 Arg/Trp+Trp/Trp基因型的个体较携带XRCC1-194 Arg/Arg基因型的个体发生肺癌的危险性升高(ORadj=1.55,95%CI:1.07-2.27,P=0.016);XRCC1-280 His/His基因型携带者较XRCC1-280 Arg/Arg+Arg/His基因型携带者发生肺癌的危险性升高(ORadj=2.21,95%CI:1.05-4.52,P=0.026)。CYP1A1-Msp1、GSTT1、mEH-exon4及XRCC1-399多态基因型在病例组与对照组中的分布频率差异均无统计学意义(P>0.05)。结论河南省人群中CYP1A1、GSTM1、GSTT1、mEH和XRCC1基因的分布与国内外相关报道有一定差异,其中CYP1A1-exon7、GSTM1、mEH-exon3、XRCC1-194及XRCC1-280基因位点的变异与河南省人群肺癌患癌危险度增高有关。     

体内有机氯农药残留水平与CYP1A1、GSTM1、GSTT1基因多态性的交互作用对女性乳腺癌发病的影响

[目的]探讨体内有机氯农药残留水平与CYP1A1、GSTM1、GSTT1基因多态性的交互作用对女性乳腺癌发病的影响。[方法]用1︰1配比的病例对照研究方法,自2006年9月～2007年10月收集女性乳腺癌病例及对照共70对。采用气相色谱法(GB/T5009.19-2003)检测血清中有机氯农药残留水平,用聚合酶链反应(PCR)检测细胞色素P4501A1Msp I(CYP1A1Msp I)、谷胱甘肽S-转移酶M1(GSTM1)和谷胱甘肽S-转移酶T1(GSTT1)3个位点的基因多态性。[结果]携带CYP1A1Msp I突变等位基因与有机氯农药(HCH/DDT)高残留存在交互作用,交互作用系数γ分别为1.558和8.491;携带GSTT1缺失型基因与DDT高残留存在交互作用,交互作用系数γ为1.726。[结论]CYP1A1Msp I突变基因型、GSTT1缺失基因型对有机氯农药的残留效应有放大作用。     

体内有机氯农药残留水平与CYP1A1、GSTMl、GSTT1基因多态性的交互作用对女性乳腺癌发病的影响

[目的]探讨体内有机氯农药残留水平与CYP1A1、GSTM1、GSTT1基因多态性的交互作用对女性乳腺癌发病的影响. [方法]用1:1配比的病例对照研究方法,自2006年9月～2007年10月收集女性乳腺癌病例及对照共70对.采用气相色谱法(GB/TS009.19-2003)检测血清中有机氯农药残留水平,用聚合酶链反应(PCR)检测细胞色素P4501A1 Msp Ⅰ(CYP1A1 Msp Ⅰ)、谷胱甘肽S-转移酶M1(GSTM1)和谷胱甘肽S-转移酶T1(GSTT1)3个位点的基因多态性.[结果]携带CYP1A1 MspⅠ突变等位基因与有机氧农药(HCH/DDT)高残留存在交互作用,交互作用系数γ分别为1.558和8.491;携带GSTT1缺失型基因与DDT高残留存在交互作用,交互作用系数γ为1.726. [结论]CYP1A1 MapⅠ突变基因型、GSTT1缺失基因型对有机氯农药的残留效应有放大作用.     

湖南人群CYP1A1、GSTM1、GSTT1基因多态性与急性白血病易感性关系研究

目的分析生物代谢酶Ⅰ相酶细胞色素P4501A1（CYP1A1）和Ⅱ相酶谷胱甘肽转硫酶GSTM1、GSTT1基因的遗传多态在湖南人群急性白血病患者和健康人群中的分布。方法采用病例对照研究方法，应用聚合酶链反应及聚合酶链反应-限制性片段长度多态性技术对112例急性淋巴细胞性白血病（ALL）患者和120例急性非淋巴细胞性白血病（ANLL）患者以及204名健康个体的CYP1A1 MspⅠ多态（3801 T—C突变）、GSTM1和GSTT1等基因的多态分布进行分析。结果ALL组与ANLL组的CYP1A1基因3801位点等位变异的频率分别为74．1％、70．8％，高于对照组（63．3％），但其差异无统计学意义（P〉0．05）；ALL组GSTM1缺失基因型（GSTM1-／-）的频率为60．7％，与对照组（55．4％）比较差异无统计学意义（P〉0．05）；ANLL组GSTM1-／-基因型频率为68．3％，与对照组比较差异有统计学意义（P〈0．05）。ALL组、ANLL组及对照组的GSTT1缺失基因型（GSTT1-／-）的频率分别为50．9％、55．0％和49．0％，病例组与对照组差异无统计学意义（P〉0．05）。GSTM1-／-和GSTT1-／-联合基因型在ALL、ANLL患者组和对照组中的频率分别为33．0％、40．0％和27．5％，其中ANLL组与对照组比较，其差异有统计学意义（P〈0．05）。同时携带CYP1A1 MspⅠ多态突变基因型（杂合突变型或纯合突变型）与GSTM1-／-、GSTT1-／-基因型的个体患ANLL的风险增加（OR=1．890，95％CI：1．084～3．295）。结论单一的CYP1A1 MspⅠ多态突变基因型或GSTT1-／-基因型与急性白血病易感性不相关；GSTM1-／-基因型及其与GSTT1-／-基因型、CYP1A1 MspⅠ多态突变基因型（杂合突变型或纯合突变型）同时存在时增加患ANLL的风险。提示GSTM1-／-可能是ANLL发病的易感因素之一，且与其他缺陷基因型存在协同作用。     

GSTT1及CYP1A1基因多态性与肺癌易感性关系

目的 探讨细胞色素P4501A1(CYP1A1)和谷胱甘肽硫转移酶T1(GSTT1)基因多态性与肺癌易感性的关系.方法 用等位特异性PCR(AS-PCR)及多重PCR技术分析106例肺癌患者和250名健康人的CYP1A1、GSTT1基因多态性、基因型分布频率和交互作用.结果 携带CYP1A1(Val/Val)/GSTT1(-)基因型的人患肺癌的风险明显增加(P=0.025);吸烟与肺癌易感性有关(P=0.037),吸烟者患肺癌的风险明显增加(OR=1.628.95%CI=1.028～2.577);携带CYP1A1(Val/Val)基因的吸烟者较携带CYP1A1(Ile/Ile)基因型的不吸烟者易患肺癌(P=0.033);携带GSTT1(-)的吸烟者患肺癌的风险明显增加(P=0.045).结论 CYP1A1突变型和GSTT1(-)基因型是肺癌的可疑易患因素,二者对肺癌的发生有协同作用,但单独携带CYP1A1突变型或GSTT1(-)基因型肺癌易感性差异无统计学意义,吸烟与肺癌易感性有关;CYP1A1突变型、GSTT1(-)基因型与吸烟在肺癌的发生上有相互促进作用.     

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。     

Effects of the GSTM1 and GSTT1 polymorphisms on the relationship between maternal exposure to environmental tobacco smoke and neonatal birth weight

The purpose of the investigation was to determine whether genetic polymorphisms in enzymes that metabolize exogenous chemicals modulate the effects of environmental tobacco smoke (ETS) exposure on birth weight. A survey was conducted from 2000 to 2001 among 266 pregnant women who were hospitalized for delivery and on their singleton live births. We determined maternal GSTM1 and GSTT1 polymorphisms by polymerase chain reaction and measured the urinary cotinine of pregnant women at delivery by radioimmunoassay. Birth weight was found to decrease significantly with increasing concentrations of maternal urinary cotinine (P < 0.05). The interactive effect of exposure to ETS and the presence of the GSTT1 polymorphism was found to be significant by multivariate analysis (P < 0.01), whereas the interactive effect of exposure to ETS and the presence of GSTM1 polymorphism did not reach statistical significance (P = 0.21). A combination of the GSTM1-null and the GSTT1 null-genotypes was found to exacerbate the effect of maternal exposure to ETS on birth weight more than the presence of either genotype alone. Our data indicate that maternal exposure to ETS negatively affects neonatal birth weight, and the adverse effect of maternal exposure to ETS on neonatal birth weight could be modified by the maternal metabolic genotypes, GSTM1 and GSTT1.     

Xenobiotic-metabolizing genes and small-for-gestational-age births: interaction with maternal smoking

BACKGROUND: Little is known about the role of xenobiotic-metabolizing gene variants as risk factors for small-for-gestational-age (SGA) births or as modifiers for the effects of exposures such as maternal smoking. METHODS: We conducted 2 joint studies: a case-control design including 493 cases (birth weight below the 10th percentile according to gestational age and sex) and 472 controls (at or above the 10th percentile) and a family-based study (mother, father, and newborn) with approximately 250 case trios and a similar number of control trios. Logistic regression and a log-linear model were used to analyze the association between genetic variants such as CYP1A1*2A, CYP1A1*2B, CYP1A1*4, GSTT1, GSTM1, and XRCC3 and SGA. The interaction between genetic variants and maternal smoking was also studied. RESULTS: The odds ratio (OR) for the association of complete maternal GSTT1 deletion with SGA was 0.63 (95% confidence interval = 0.41-0.97), and that for the complete newborn GSTM1 deletion was 0.74 (0.55-0.98). Newborns with the partial GSTT1 deletion had an OR of 1.40 (1.01-1.95), and newborns homozygous for CYP1A1*2A had an OR of 4.28 (1.02-18.0). These results were coherent with the trio-based results. Significant interactions were observed between maternal smoking in the third trimester and CYP1A1*2A (P = 0.03), XRCC3 (P = 0.03), and newborn GSTT1 (P = 0.01). CONCLUSIONS: Certain genetic variants involved in the metabolism of xenobiotics increase the risk of SGA, as well as modify the effects of maternal smoking by increasing or decreasing its risk.     

微粒体环氧化酶与谷胱甘肽S转移酶的遗传多态性对新生儿出生体重的影响

「目的」探讨母亲微粒体环氧化酶（ＥＰＨＸ１）与谷胱甘肽Ｓ转移酶（ＧＳＴＭ１，ＧＳＴＴ１）的遗传多态笥对新生儿出生体重的影响。「方法」采用回顾性流行病学调查方法，使用统一调查表，由经过培训的调查员在北京燕山某医院对入院分娩的６３０个母亲婴儿对进行调查。「结果」单因素分析发现：ＥＰＨＸ１和ＧＳＴＴ１、ＧＳＴＭ１基因多态对新生儿出生体重的影响无显著意义。经母亲年龄、文化程度、生育史、芳香烃溶剂暴露、在家     

基因多态性与血清p53蛋白过表达的关系

目的　探讨细胞色素P4 5 0 1A1(cytochromeP4 5 0 1A1,CYP1A1)和谷胱甘肽转硫酶M1(GlutathioneS -trans ferasesM1,GSTM1)基因多态性与血清p5 3蛋白过表达之间的关系。方法　以 12 7名血清p5 3蛋白过表达阳性者为病例组 ,以 12 7名血清p5 3蛋白阴性者为对照组 ,分别采用多重差异PCR(multi-differentialPolymerasechainreaction ,MD -PCR)检测外周血淋巴细胞GSTM1的缺失和采用等位特异PCR(allele -specificPoly -merasechainreaction ,AS -PCR)检测外周血淋巴细胞CYP1A1基因的等位变异 ,采用 χ2 检验来比较GSTM1和CYP1A1的多态性的差异。结果　单独分析CYP1A1和GSTM1基因多态性在 2组中的分布没有显著性差异 (P >0 0 5 ) ,但GSTM1基因缺失型即GSTM1(- )和CYP1A1基因纯合突变型即CYP1A1Val/Val基因型联合增加了血清p5 3蛋白过表达的危险性 (P <0 0 5 ) ,OR及 95 %CI为 3 86 (0 95～ 15 5 9)。结论　CYP1A1和GSTM1的等位变异联合增加了血清p5 3蛋白过表达的危险性。     

Association of self-reported passive smoking in pregnant women with cotinine level of maternal urine and umbilical cord blood at delivery

Passive smoking during pregnancy leads to adverse effects on mother and infant. The present investigation was designed to evaluate the association between maternal reported passive smoking with the cotinine concentration of maternal urine and umbilical cord blood at delivery and to determine the accuracy of maternal reporting of exposure to cigarette smoke during pregnancy. This was a cross-sectional study. From the 108 non-smoker pregnant women who were referred for delivery, 54 were passive smokers. Urine samples were collected from the mothers in the delivery room and blood samples after birth were taken from the umbilical cord. Passive smoking was evaluated through questionnaire and cotinine level of urine and umbilical cord blood. The geometric mean cotinine concentration of the maternal urine and the umbilical cord serum were, respectively, 27.4 ± 29.96 ng/mL and 3.71 ± 1.22 ng/mL in the exposed group (P < 0.001) and 0.75 ± 2.29 and 0.40 ± 0.63 in the non-exposed group (P < 0.001). There was a statistically significant correlation between maternal urinary and umbilical cord serum level of cotinine (P < 0.001, r = 0.58). Significant associations were shown between maternal reports of exposure to cigarette smoking with cotinine level of urine (kappa = 96%) and umbilical cord (kappa = 98%) (P < 0.001). This study shows that the pregnant woman's report of passive smoking during pregnancy in Iran is accurate. The questionnaire is an appropriate method to evaluate smoke exposure and could replace cotinine measurement.     

代谢酶基因多态性对孕期妇女尿中1-羟基芘水平的影响

目的 探讨代谢酶基因多态性对孕期妇女尿1-羟基芘(1-OHPy)水平的影响.方法 于2006年10月-2008年1月,在太原市两所二级甲等综合性医院中随机调查符合条件的孕期妇女347名,进行流行病学调查和生物样品的收集.采用高效液相色谱法测定尿样中1-羟基芘水平,应用多重PCR和限制性内切酶PCR(RFLP-PCR)技术分析四种代谢酶基因多态性(GSTM1,GSTT1,GSTP1,CYP1A1 Msp I).结果 校正年龄、教育水平等因素后,携带CYP1A1纯合突变基因型的孕期妇女其尿样1-OHPy水平(1.653 0 μmol/mol Cr)明显高于野生型(1.162 4 μmol/mol Cr),差异有统计学意义(P=0.047);携带GSTP1纯合突变基因型的孕期妇女尿样1-OHPy水平(1.1721μmol/mol Cr)明显高于野生型(0.8679μmol/mol Cr).差异有统计学意义(P=0.009);多基因模型中,CYP1A1和GSTP1对孕期妇女尿样1-OHPy浓度具有修饰作用(P=0.046,P=0.029),多基因模型的决定系数为0.262;基因-基因交互作用分析显示对尿中1-OHPy浓度有修饰作用的多态位点主要有CYP1A1和GSTM1.结论 代谢酶基因多态性在PAHs体内代谢中具有修饰作用,CYP1A1、GSTP1基因多态性对于孕期妇女体内芘代谢中可能起着重要作用,CYP1A1与GSTM1对芘的代谢具有交互作用.