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).     

GSTM1和GSTT1基因多态性与女性肺癌易感性的关系

目的：探讨谷胱苷肽硫转移酶M1（glutathione S-transferaseM1,GSTM1)和T1（glutathione S-transferaseT1,GSTT1)基因多态性与女性肺癌遗传易感性的关系。方法：采用病例－对照研究方法和多重PCR技术检测女性肺癌病例组42人和健康对照组55人的GSTM1和GSTT1基因缺陷型的频率，并评价GSTM1和GSTT1基因型以及他们之间的交互作用与肺癌遗传易感性的关系。结果：在本次研究的人群中，病例组GSTM1和GSTT1基因缺陷型的频率分别为66．7％和45．2％，对照组为54．5％和38．2％，GSTM1基因缺陷型和GSTT1基因缺陷型的频率在病例组和对照组之间均无显性差异（P＞0．05）。在不吸烟的女性人群中，GSTM1基因缺陷型携带患肺癌的危险性是GSTM1基因功能型携带的2．557倍（P＝0．046）；GSTT1基因缺陷型则有女性肺癌的发生无显关联（P＝0．557）。此外，GSTT1基因型与GSTM1基因型之间亦无明显的交互作用（P＞0．05）。结论：GSTM1基因缺陷型可能是非吸烟女性患肺癌的重要危险因素。GSTT1基因缺失则可能与肺癌的发生无关，在女性肺癌的发生过程中GSTM1和GSTT1可能不存在交互作用。     

The role of glutathione S-transferase M1 and T1 gene polymorphisms and fruit and vegetable consumption in antioxidant parameters in healthy subjects

The correlation of glutathione S-transferase (GST) M1/T1 genetic polymorphisms with oxidative stress-related chronic diseases was proved recently. The aim of the present study was to investigate the association of GSTM1/T1 genetic polymorphisms with antioxidant biomarkers and consumption of fruits and vegetables (F&V) in healthy subjects. In this study, for conducting a 3 d dietary survey, 190 healthy adults were recruited. After DNA extraction, a multiple PCR method was used for GSTM1/T1 genotyping. A spectrophotometer method was applied for the determination of plasma total antioxidant capacity (T-AOC), vitamin C level and erythrocyte GST enzyme activity. A general linear model was used to compare the mean values of antioxidant parameters for different GSTM1/T1 genotypes and consumption of F&V. Polymorphisms of GSTM1/T1 had no effects on plasma T-AOC and vitamin C levels. Deletion of the GSTM1 gene decreased the erythrocyte GST activity. There was correlation between plasma T-AOC and consumption of F&V in the GSTM1? or GSTT1? subjects. A similar pattern was evident for erythrocyte GST activity in the GSTM1? subjects. No association was found among consumption of F&V and GSTM1/T1 genotypes and plasma vitamin C level. Different consumption of F&V had no impact on plasma T-AOC and vitamin C levels in the GSTM1?/GSTT1? or GSTM1?/GSTT1? subjects. The erythrocyte GST activity was more sensitive to consumption of F&V in the individuals with the GSTM1?/GSTT1? genotype. Association was found among GSTM1/T1 genotypes, antioxidant parameters and consumption of F&V. Large-scale and multiple ethnic studies are needed to further evaluate the relationship.     

GSTM1, GSTT1, and GSTP1 polymorphisms, breast cancer risk factors and mammographic density in women submitted to breast cancer screening

Genetic polymorphisms in genes related to the metabolism of xenobiotics, such as genes of the glutathione S-transferases (GSTM1, GSTT1, and GSTP1) superfamily have been associated with an increased risk for breast cancer (BC). Considering the high incidence of BC in the city of Porto Alegre in southern Brazil, the purpose of this study was to characterize genotypic and allelic frequencies of polymorphisms in GSTM1, GSTT1, and GSTP1, and correlate these molecular findings with established risk factors for breast cancer including mammographic density, in a sample of 750 asymptomatic women undergoing mammographic screening. Molecular tests were performed using the multiplex polymerase chain reaction (PCR) for GSTM1 and GSTT1, and quantitative PCR for GSTP1 polymorphisms. Overall, the frequencies of GSTM1 and GSTT1 null genotypes were 45% and 21%, respectively. For GSTP1 polymorphism, genotypic frequencies were 44% for the Ile/Ile genotype, 44% for the Ile/Val genotype, and 12% for Val/Val genotype, with an allelic frequency of 66% for the wild type allele in this population, similar to results of previous international publications. There was a statistically significant association between the combined GSTM1 and GSTT1 null genotypes (M-/T-) and mammographic density in post menopausal women (p = 0.031). When the GSTT1 null (T-) genotype was analyzed isolated, the association with mammographic density in post menopausal women and in the overall sample was also statistically significant (p = 0.023 and p = 0.027, respectively). These findings suggest an association of GSTM1 and GSTT1 null genotypes with mammographic density.     

Determinants of aflatoxin levels in Ghanaians: sociodemographic factors, knowledge of aflatoxin and food handling and consumption practices

Aflatoxins are among the most potent of carcinogens found in staple foods such as groundnuts, maize and other oil seeds. This study was conducted to measure the levels of aflatoxin B(1) (AFB(1)) albumin adducts in blood and aflatoxin M(1) (AFM(1)) metabolite in urine of people in a heavy peanut and maize consuming region of Ghana and to examine the association between aflatoxin levels and several socio-demographic factors and food handling and consumption practices. A cross-sectional study was conducted in four villages in the Ejura Sekyedumase district of Ghana. A socio-demographic survey was administered to 162 participants. Blood samples were collected from 140 and urine samples from 91 of the participants and AFB(1) albumin-adduct levels in blood and AFM(1) levels in urine were measured. High AFB(1) albumin-adduct levels were found in the plasma (mean+/-SD=0.89+/-0.46pmol/mg albumin; range=0.12-3.00pmol/mg; median=0.80pmol/mg) and high AFM(1) levels in the urine (mean+/-SD=1,800.14+/-2602.01pg/mg creatinine; range=non-detectable to 11,562.36pg/mg; median=472.67pg/mg) of most of the participants. There was a statistically significant correlation (r=0.35; p=0.007) between AFB(1)-albumin adduct levels in plasma and AFM(1) levels in urine. Several socio-demographic factors, namely, educational level, ethnic group, the village in which participants lived, number of individuals in the household, and number of children in the household attending secondary school, were found to be significantly associated with AFB(1) albumin-adduct levels by bivariate analysis. By multivariate analyses, ethnic group (p=0.04), the village in which participants live (p=0.02), and the number of individuals in the household (p=0.01), were significant predictors of high AFB(1) albumin-adducts. These findings indicate strongly that there is need for specifically targeted post-harvest and food handling and preparation interventions designed to reduce aflatoxin exposure among the different ethnic groups in this region of Ghana.     

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.     

Carnitine alters binding of aflatoxin to DNA and proteins in rat hepatocytes and cell-free systems.

The objective of this study was to determine effects of L-carnitine on aflatoxin B(1) (AFB(1))-DNA adduct formation in isolated rat hepatocytes, its dose response, specificity and mode of action. All experiments were conducted in either freshly isolated rat hepatocytes or cell-free systems. There was negative linear correlation between the dosage of carnitine and formation of [(3)H]AFB(1)-DNA adducts in the hepatocytes; however, the partitioning of AFB(1) into cellular compartments was not affected by carnitine. The attenuating effect of carnitine on AFB(1)-DNA adduct formation was also present in a cell-free system, but there was lack of specificity because acetylcarnitine and gamma-aminobutyric acid (GABA) were equally effective. Carnitine appears to interfere with bioactivation of AFB(1) and binding of AFB(1)-epoxide to DNA. On the contrary, carnitine enhanced the binding of AFB(1) and its epoxide to microsomal proteins, plasma proteins and bovine serum albumin. These results indicate that carnitine diverts AFB(1)-epoxide away from DNA by promoting binding to proteins. We conclude that modulation of AFB(1) binding to proteins and DNA by carnitine alters the carcinogenic and hepatotoxic potential of AFB(1) and poses concerns about the human AFB(1)-exposure data based on the AFB(1)-albumin adduct concentrations as a biomarker.     

Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk

Cruciferous vegetables contain anticarcinogenic isothiocyanates (ITCs), particularly the potent sulforaphane, which may decrease risk of prostate cancer through induction of phase II enzymes, including glutathione S-transferases (GSTs). We evaluated this hypothesis in a population-based, case-control study of prostate cancer, including 428 men with incident prostate cancer and 537 community controls. An in-person interview included an extensive food-frequency questionnaire. Genotyping for deletions in GSTM1 and GSTT1 was performed in a subset of men who provided blood. Intakes of cruciferous vegetables and of broccoli, the greatest source of sulforaphane, were associated with decreased prostate cancer risk at all levels above the lowest consumers [adjusted 4th quartile odds ratio (OR)=0.58; 95% confidence interval (CI)=0.38, 0.89, and 0.72 (95% CI=0.49, 1.06)], respectively. In relation to genotypes, there was a nonsignificant increase in risk with the GSTT1 null genotype (OR=1.51; 95% CI=0.98, 2.31) but no effects of GSTM1 genotype. However, men with GSTM1-present genotype and high broccoli intake had the greatest reduction in risk (OR=0.49; 95% CI=0.27, 0.89). Our findings provide evidence that two or more servings per month of cruciferous vegetables may reduce risk of prostate cancer, especially among men with GSTM1-present alleles, and are consistent with a role of dietary ITCs as chemopreventive agents against prostate cancer.     

GSTM1和GSTT1基因多态性与大气污染的交互作用对哮喘的影响

目的研究GSTM1和GSTT1基因多态性与大气污染的交互作用对哮喘发病的影响,为哮喘的预防、诊断和治疗提供理论依据.方法在大气污染程度不同的重污染区和轻污染区分别选择21和33例哮喘患者;同时分别选择性别相同、年龄相近、居住地区相同的19和34例非呼吸系统疾病患者为对照组,运用PCR技术进行GSTM1和GSTT1基因型分布检测,并进行流行病学调查.结果哮喘病例组和对照组GSTM1野生型和突变型的构成比分别为33.3%,66.7%和47.2%,52.8%,差异无统计学意义;GSTT1野生型和突变型的构成比分别为46.3%、53.7%和47.2%、52.8%,差异无统计学意义(P＞0.05).在大气污染相对较轻的情况下,GSTM1基因呈突变型的人群哮喘发病危险性是野生型基因携带者的2.667倍;暴露于大气重污染环境中的GSTM1基因呈野生型的人群哮喘发病危险是暴露于大气轻污染环境中GSTM1基因呈野生型的人群的2.125倍;既暴露于大气重污染环境中,而GSTM1基因又呈突变型的人群哮喘发病危险是暴露大气轻污染环境中GSTM1基因呈野生型的人群的2.061倍,但差异无统计学意义(P＞0.05).结论该研究尚未发现GSTM1、GSTT1基因多态性和大气污染的交互作用对哮喘发病有显著性影响.     

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。     

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。     

厦门市不同吸烟类型与其他危险因素致肝癌效应修饰作用

目的 评价不同类型吸烟暴露的单独效应,并分析吸烟在肝癌发病中的效应修饰作用.方法 采用病例对照研究方法,对345例肝癌病例和961例健康对照进行危险因素调查,采集血液标本进行HBsAg、抗-HCV和黄曲霉毒素(AFB1)白蛋白加合物等含量的检测,针对潜在的危险因素应用多元logistic回归分析评价调整的危险比(AOR)和95%CI.结果 女性被动吸烟暴露与肝癌有关联(AOR=2.35,95%CI:1.19～4.07);男性规律的吸烟与肝癌有关联(AOR=2.27,95%CI:1.14～3.31).在男性,吸烟与慢性乙肝病毒感染有正相关交互作用,交互效应超额相对危险比(RERI)为98.70,归因交互效应百分比(AP)为81.0%(u=2.11,P=0.02);在女性,吸烟与血清AFB1白蛋白加合物浓度有正相关交互作用,交互效应RERI为2.69,归因交互效应AP为50.0%(u=2.60,P=0.01).结论 吸烟与肝癌的关联性有性别差异,尤其是在慢性病毒感染和具有较高浓度的AFB1白蛋白加合物浓度的人群中应控制吸烟.     

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。     

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.     

Ethylene oxide-protein adduct formation in humans: influence of glutathione-S-transferase polymorphisms

Objective: The influence of the polymorphic human glutathione-S-transferase (GST) T1 and M1 genotypes (classified as “conjugators” and “nonconjugators”) on the biological effects of nonoccupational ethylene oxide exposure as reflected by the formation of globin N ²-hydroxyethylvaline adducts was investigated. Specific attention was paid to smoking as a potential source of exposure. A total of 27 Caucasian subjects, including 10 women and 17 men, participated in the study. Volunteers were grouped as smokers, i.e., 6 subjects (5 male, 1 female), and nonsmokers, i.e., 21 subjects (12 male, 9 female). The regular cigarette consumption in the smoker group ranged from 10 to 25 cigarettes/day. Methods: The amount of N ²-hydroxyethylvaline (HEV) bound to the N-terminal valine in human globin was determined following a procedure described by Bader and co-workers and the Deutsche Forschungsgemeinschaft. The GST genotypes were determined by a polymerase chain reaction (PCR) analysis outlined by Bell and colleagues (with β -globin serving as an internal standard) and Kempkes and co-workers (coamplification of the GSTT1 fragment). Results: The median level of HEV detected in the smoker group was 280 pmol/g globin as compared with the median value of 50 pmol/g globin recorded for the nonsmokers, indicating that ethylene oxide intake from cigarettes may result in a ∼5-fold higher overall HEV level in smokers in comparison with nonsmoking individuals. No dose-effect correlation was observed between daily cigarette consumption and the resulting HEV levels. Moreover, the individual GSTT1 or GSTM1 genotype did not influence the HEV level in smokers. The subgroup of nonsmoking GSTT1 conjugators revealed a median HEV value of 46 pmol/g globin as compared with the median value of 92 pmol/g globin found in the nonconjugator subgroup. Subjects with the GSTM1 gene had a median HEV value of 55 pmol/g globin, whereas subjects with the gene deletion had a median HEV value of 44 pmol/g globin. The 2-fold increase in the median HEV value detected in GSTT1 non-conjugators as compared with GSTT1 conjugators indicates an influence of GSTT1 on the globin HEV levels. This hypothesis was found to be significant in the nonparametric Mann-Whitney U-test for independent samples (P < 0.002, two-sided). The same test was applied to evaluate the influence of GSTM1 on the globin HEV levels. No significant influence was observed (P > 0.10; two-sided). Conclusions: This result is in accordance with the finding that ethylene oxide is a substrate for GSTT1 but not for GSTM1. In addition, this study demonstrates a clear influence of genetically determined GSTT1 status on biological effects, e.g., protein adduct formation after non-occupational ethylene oxide exposure. In smokers, however, a modulating influence of GSTT1 status was not observed. Received: 29 December 1997 / Accepted: 27 June 1998     

GSTT1基因、GSTM1基因多态性与乳腺癌易感性的病例-对照研究

目的探讨女性乳腺癌人群中,雌激素代谢酶GSTT1基因、GSTM1基因多态性与乳腺癌易感性的关系。方法采用聚合酶链反应(PCR)对天津市105例正常对照者和100例乳腺癌患者的GSTT1基因、GSTM1基因多态性进行检测,Logistic回归分析评估单个、联合基因以及雌激素暴露相关因素对罹患乳腺癌的危险度。结果GSTT1基因缺失型在两组间分布频率的差别有统计学意义(χ2=13.766,P=0.000),GSTM1基因在两组间分布频率的差别有统计学意义(χ2=13.135,P=0.000);联合基因型分析显示,随着GSTT1或GSTM1基因型缺失情况的出现,个体罹患乳腺癌的危险性增加(趋势性检验,χ2=27.011,P=0.000);GSTM1基因和GSTT1基因同时缺失的人群OR(95%CI)为12.338(3.621～22.042);多因素非条件Logistic回归分析结果显示:GSTT1基因和GSTM1基因缺失与乳腺癌的发生相关。结论雌激素代谢酶相关基因多态性与乳腺癌发生相关。     

Effects of APOE rs429358, rs7412 and GSTM1/GSTT1 Polymorphism on Plasma and Erythrocyte Antioxidant Parameters and Cognition in Old Chinese Adults

Apolipoprotein E (APOE) and oxidative damage were correlated with the risk of Alzheimer’s disease (AD). Glutathione S-transferase (GST) polymorphism was proved to be associated with body antioxidant capacity and involved in the oxidative damage related chronic diseases. To explore the combined effects of APOE rs429358, rs7412 and GSTM1/T1 polymorphism on antioxidant parameters and cognition in old Chinese adults, a community-based cross-sectional study was carried out in 477 Chinese adults aged from 55 to 75. Information on demography and lifestyle of the participants was collected with a questionnaire. Cognitive function was measured by using a Montreal Cognitive Assessment (MoCA) test. Fasting venous blood samples were collected for APOE rs429358, rs7412 and GSTM1/T1 genotyping, and parameter measurement. No association of APOE rs7412, rs429358 and GSTM1/T1 polymorphisms with cognition was detected in the old Chinese adults. APOE rs429358, rs7412 polymorphism was mainly associated with plasma α-tocopherol, low density lipoprotein cholesterol (LDL-C) and plasma total antioxidant capacity (T-AOC) levels (p < 0.05). Interaction of APOE rs429358 and GSTT1 genotype on the plasma triglyceride (TG) level and erythrocyte catalase (CAT) and GST enzyme activities were detected (p < 0.05). The subjects with APOE rs429358 T/C + C/C and GSTT1− genotype were found to have the highest plasma TG level, erythrocyte CAT enzyme activity, and the lowest GST enzyme activity compared to subjects with other genotypes (p < 0.05). Lowest erythrocyte CAT enzyme activity and highest glutathione peroxidase (GSH-Px) enzyme activity were detected in the subjects with APOE rs7412 T/C + T/T and GSTM1+ genotype as compared with subjects with other genotypes. The levels of plasma and erythrocyte antioxidant parameters were APOE genotype associated. GSTM1 or GSTT1 genotype modified the influence of APOE rs7412, rs429358 polymorphism on antioxidant parameters.     

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.     

中国人群谷胱甘肽转移酶M1和T1的基因多态性分析:系统综述及吉林省结核涂阳人群研究

目的 了解谷胱甘肽转移酶M1(GSTM1)和T1(GSTT1)基因多态性在中国人群及吉林省结核涂阳人群中的分布.方法 采用系统综述方法,以"GSTM1/GSTT1+多态性"为关键词搜索国内发表于2009年1月以前、研究类型为横断面研究或队列研究基线的文献,经综合分析获得GSTM1、GSTT1基因多态性分布信息.以吉林省14个县(区)2007年11月至2008年5月间的全部结核涂阳病例(共1120名)为研究对象,采用多重PCR法检测GSTM1、GSTT1基因型.结果 系统综述得到中国人群GSTM1、GSTT1基因纯合缺失型和GSTM1-GSTT1联合缺失基因型频率分别为54.2%、46.8%和26.2%,其中以汉族为主的人群分别为53.4%、44.9%和25.5%;本研究中吉林省结核涂阳人群相应频率分别为57.2%、20.4%和13.7%,GSTM1、GSTT1基因型及组合基因型分布的性别、年龄差异无统计学意义(P>0.05).与系统综述结果相比,本研究人群GSTM1纯合缺失基因型频率偏高(P=0.016),GSTT1纯合缺失基因型和GSTM1-GSTT1联合缺失基因型频率明显偏低(P值均<0.001).结论 GSTM1、GSTT1基因多态性分布存在种族差异;本研究人群结果与系统综述结果的统计学差异可能是由于前者样本量较大、既往研究对象多为南方人群所致.