CYP2E1,GSTM1基因多态性与甘肃地区食管癌易感性

目的探讨细胞色素氧化酶P450,GSTM1的基因多态性与甘肃地区食管癌遗传易感性之间的以及基因—基因的交互作用。方法运用病例对照分子流行病学研究方法和聚合酶链反应方法对食管癌病例组和正常对照组基因DNA进行CYP2E1,GSTM1基因分型。结果CYP2E1基因pst1多态性的三种基因型在食管癌组和对照组的频率差异有统计学意义（χ2=12.59,P〈0.05）。携带C1/C1基因型个体发生食管癌的风险是携带其他基因型2.80倍（OR=2.80,95%C I=1.21-6.46）。食管癌组GSTM1（-）基因型频率显著高于对照组（χ2=10.292,P〈0.05）,携带GSTM1（-）的个体患食管癌的危险性显著高于GSTM1（＋）基因型的个体（OR=2.337,95%C I=1.39-3.93）。联合分析CYP2E1基因pst1多态性和GSTM1基因多态性,携带有C1/C1和GSTM1（-）基因型的个体患食管癌的风险高于携带GSTM1（＋）和C1/C2或C2/C2基因型的个体（OR=3.00,95%C I=1.7375-5.182）。结论CYP2E1,GSTM1基因多态性与食管癌易感性有关联,CYP2E1基因C1/C1基因型是食管癌的易感性基因,而GSTM1基因缺失使食管癌危险性增加,CYP2E1,GSTM1存在交互作用。     

代谢酶NAT2基因多态性与肺癌易感性关系的研究

目的 探讨代谢酶N-乙酰化转移酶2(NAT2)基因多态性与肺癌易感性的关系.方法 采用聚合酶链式反应-限制性片段长度多态性技术检测152名正常人和150例原发性肺癌患者的外周血NAT2基因型.应用病例对照研究分析NAT2基因多态性与肺癌易感性的关系.结果 ①NAT2等位基因型WT/WT、WT/Mx、Mx/Mx在对照组中分布频率分别为28.9%、52.0%和19.1%;在肺癌组中分布频率分别为22.0%、45.3%和32.7%,两组比较差异有统计学意义(P=0.023).②携带NAT2慢乙酰化基因型个体患肺癌的风险是携带NAT2快乙酰化基因型个体的1.84倍(95%CI为1.044～3.231,P=0.035).③携带慢乙酰化基因型个体患肺腺癌的风险进一步升高,是携带快乙酰化基因型个体的2.49倍(95%CJ为1.242～4.973,P=0.010).④携带NAT2慢乙酰化基因型吸烟者患肺癌的风险是携带快乙酰化基因型吸烟者的2.34倍(95%CI为1.007～5.424,P=0.048).结论 NAT2慢乙酰化基因型显著增加中国汉族人群尤其是吸烟者患肺癌的风险.     

N-乙酰基转移酶2基因多态性与结肠腺癌易感性的关系

目的探讨N-乙酰基转移酶2(NAT2)基因多态性与结肠腺癌遗传易感性的相关性。方法采用聚合酶链反应-限制性片断长度多态性(PCR-RELP)方法,检测168例结肠腺癌患者及204例健康对照者NAT2基因型和等位基因频率,分析正常人与结肠腺癌患者NAT2各等位基因频率及基因型频率的差异。结果在正常人及结肠腺癌患者中,NAT2各等位基因频率分布差异无统计学意义(P＞0．05)。但与正常对照组相比,结肠腺癌患者中慢型乙酰化基因型频率增高(42．8%比33．7%,P= 0．033,OR=1．576,95%CI：1．037～2．396)。根据不同临床特征分析,慢型乙酰化基因型频率在不同年龄结肠癌患者中差异无统计学意义(P＞0．05),但在远侧结肠癌(P=0．022,OR=2．305,95%CI：1．116～4．763)、Dukes C期(P=0．025,OR=2．065,95%CI：1．089～3．912)、低分化(P=0．031,OR=2．128,95%CI：1．065～4．251)患者中明显增高。结论NAT2慢型乙酰化基因型与结肠腺癌及与肿瘤部位、Dukes分期及分化程度显著相关。     

细胞色素CYP2A6基因多态性与COPD易感性的关系

目的探讨细胞色素CYP2A6基因多态性与COPD易感性的关系。方法应用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)检测40例COPD患者及37例健康体检者静脉血细胞色素P450 2A6位点等位基因和基因型。结果 1.COPD患者CYP2A6-163C>A位点基因缺失型(del)和野生型(wt)基因型频率为17.5%、82.5%,健康对照组分别为40.5%、59.5%,两组基因分布频率差异有统计学意义(χ2=5.000,P=0.025),携带CYP2A6wt基因型者较携带CYP2A6del基因型者患COPD风险增加(OR=0.31,95%CI=0.109-0.886,P<0.05)。2.在吸烟者中,携带CYP2A6wt基因型者较携带CYP2A6del基因型者患COPD风险增加(OR=0.24,95%CI=0.064-0.920,P<0.05),在不吸烟者中,携带CYP2A6wt、CYP2A6del基因型者之间患COPD风险无明显差异。结论 1.CYP2A6-163C>A基因多态性可能是COPD发病的危险因素。2.野生型(wt)可能为吸烟者患COPD的一个易感因素。     

N-乙酰化转移酶2基因多态性与抗结核药物所致肝损伤的相关性

目的 探讨N-乙酰化转移酶2(NAT2)基因多态性与抗结核药致肝损伤(ADIH)的相关性.方法 以抗结核治疗3个月内出现肝损伤的106例结核患者为病例组,未出现肝损伤的106例结核患者为配对对照.采用1:1匹配的病例对照研究和聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术,检测106对结核患者的NAT2基因481C/T、590G/A、857G/A位点多态性情况,并对主要环境影响因素和基因型进行单因素和多因素条件Logistic回归分析.结果 病例组NAT2基因的481C/T、590G/A、857G/A位点的T、A、A等位基因频率分别为7.5%、28.8%、17.9%,对照组分别为6.6%、18.9%、17.5%.病例组NAT2慢速乙酰化型的频率明显高于对照组,粗OR值为2.250(95%CI为1.140～4.441).对文化程度、职业、体质指数(BMI)、吸烟、饮酒和结核类型6个可疑危险因素进行了单因素分析,仅低BMI和饮酒为ADIH发生的危险因素.在多因素分析中调整BMI、饮酒两个因素后,NAT2乙酰化程度仍与ADIH的发生显著相关,调整OR值为2.246(95%CI为1.086～4.644).结论 NAT2基因慢速乙酰化型町能与ADIH的发生有关.     

载脂蛋白E基因多态性与我国人群2型糖尿病肾病相关性的Meta分析

目的 探讨糖尿病患者载脂蛋白E(ApoE)基因多态性与我国人群2型糖尿病肾病(DN)发生的相关性.方法 检索2008年6月以前ApoE基因多态性与DN相关性的相关文献,用Meta分析方法评估文献的发表偏倚,计算各项研究总的OR值.结果 与E3/3基因型携带者比较,携带E2/2、E3/2的T2DM患者发生DN的危险性OR值(95%CI)分别为2.16(1.04～4.83)、1.92(1.47～2.51).与ε3等位基因比较,携带ε2等位基因T2DM患者发生DN的危险性OR为1.76(1.41～2.19).结论 ApoE基因多态性与DN相关,其中E2/2、E3/2基因型、ε2等位基因可能是我国人群2型糖尿病患者发生DN的风险因子.     

哈萨克族食管癌与CYP2E1基因多态性及烟酒嗜好的关系

目的:探讨细胞色素P4502E1(CYP2E1)基因多态性,烟酒嗜好与哈萨克族食管癌易感性的关系.方法:采用1:2配比的病例对照研究方法,调查哈萨克族食管癌患者120例和非食管癌患者240例,采用聚合酶链-限制性片段长度多态(PCR-RFLP)方法检测CYP2E1 RsaⅠ位点的基因型.结果:病例组中CYP2E1 RsaⅠ位点C1/C1、C1/C2、C2/C2基因型频率与对照组比较(78.3%vs53.3%,19.2%vs 37.5%,2.5%vs 9.2%,X~2=21.794,P<0.01)差异有统计学意义:携带C1/C1基因型发生食管癌的危险性是携带C1/C2或C2/C2基因型的3.07倍(95%CI:1.87.5.03);交互作用提示CYP2E1基因多态与吸烟、饮酒均存在交互作用;其危险性远高于各单独作用之和.结论:CYP2E1 RsaⅠ位点基因多态性与大量吸烟、饮酒之间的基因-环境交互作用可增强哈萨克族人群患食管癌的风险.     

CYP2E1 Rsa Ⅰ/Pst Ⅰ多态性与亚洲人肺癌发病风险的关系

细胞色素P450 2E1(CYP2E1)是细胞色素P450基因家族中的重要成员,参与亚硝胺等前致癌物在体内的代谢活化.CYP2E1基因具有多态性,其中Rsa Ⅰ/Pst Ⅰ基因多态性与肺癌的危险性关系目前尚未明确,各地研究结果不一致.我们通过检索Pub Med,Embase,Web of Science和CNKI数据库中相关研究的文献,提取相关数据,采用荟萃分析量分析CYP2E1多态性与肺癌发生风险.     

载脂蛋白E基因多态性与非酒精性脂肪性肝病关系的Meta分析

目的研究载脂蛋白E(apolipoprotein E,Apo E)基因多态性与非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)发病的关系。方法全面检索和筛选相关文献,并进行Meta分析,计算OR值及95%CI,并评价其发表偏倚,运用敏感性分析评价结果的可靠性。结果实际纳入文献5篇,包括932例NAFLD患者,1 703例对照者。以野生型ε3/3基因型及等位基因ε3为参照,Meta分析研究发现,总体分析中Apo Eε2、ε4等位基因及基因型ε2/2、ε2/3、ε2/4、ε3/4、ε4/4在NAFLD患者中的分布频率与对照组比较,差异无统计学意义(P0.05)。亚组分析发现中国人群Apo E基因多态性与NAFLD发病风险无相关性,在欧洲人群的研究中,ε2/3 vsε3/3(P=0.002,OR=0.50,95%CI:0.32~0.77)、ε2等位基因携带者(ε2/2+ε2/3)vsε3/3(P=0.04,OR=0.59,95%CI:0.35~0.98),差异有统计学意义;ε2/3基因型与欧洲人群NAFLD的发生具有相关性。结论 NAFLD的发生与中国人群Apo E基因多态性无明显相关性,但ε2/3基因型可能是欧洲人群NAFLD的保护因素。     

Relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh＇s esophageal squamous cell cancer in Xinjiang, China

AIM: To analyze the relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh's esophageal squamous cell cancer in China. METHODS: The genotypes of cytochromes P450 (CYP) 2E1 and glutathione S-transferase (GST) M1 were investigated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) following PCR in 104 Kazakh's patients with esophageal cancer (EC) and 104 non-cancer controls. RESULTS: The frequency of CYP2E1 c1/c1 genotype was significantly higher in patients with cancer (77.9%) than in control subjects (24.0%) (P<0.05; OR, 11.13; 95%CI, 5.84-21.22). The difference of GSTM1 null was significantly more frequent in the cancer (34.6%) vs the control group (3.8%) (P<0.05; OR, 13.24; 95%CI, 4.50-38.89). On the other hand, the combination of GSTM1 presence and CYP2E1 c1/c1 genotypes increased the risk for cancer (P<0.05; OR, 13.42; 95%CI, 6.29-28.3). CONCLUSION: The CYP2E1 c1/c1, GSTM1 deletion genotypes are genetically susceptible biomarkers for ESCC in Kazakh population. Individuals with allele c1 of RsaI polymorphic locus for CYP2E1 may increase the risk of ESCC. Moreover, CYP2E1 wild type (c1/c1) increased the susceptibility to ESCC risk in Kazakh individuals with GSTM1 presence genotype.     

Cytochrome P450 2E1 genotype and the susceptibility to antituberculosis drug-induced hepatitis

Most cases with antituberculosis drug-induced hepatitis have been attributed to isoniazid. Isoniazid is metabolized by hepatic N-acetyltransferase (NAT) and cytochrome P450 2E1 (CYP2E1) to form hepatotoxins. However, the role of CYP2E1 in this hepatotoxicity has not yet been reported. The aim of this study was to evaluate whether the polymorphism of the CYP2E1 gene is associated with antituberculosis drug-induced hepatitis. A total of 318 tuberculosis patients who received antituberculosis treatment were followed prospectively. Their CYP2E1 and NAT2 genotypes were determined using a polymerase chain reaction with restriction fragment length polymorphism method. Twenty-one healthy volunteers were recruited for CYP2E1 phenotype study using a chlorzoxazone test. Forty-nine (15.4%) patients were diagnosed to have drug-induced hepatotoxicity. Patients with homozygous wild genotype CYP2E1 c1/c1 had a higher risk of hepatotoxicity (20.0%; odds ratio [OR], 2.52) than those with mutant allele c2 (CYP2E1 c1/c2 or c2/c2, 9.0%, P =.009). If CYP2E1 c1/c2 or c2/c2 genotype combined with rapid acetylator status was regarded as the reference group, the risk of hepatotoxicity increased from 3.94 for CYP2E1 c1/c1 with rapid acetylator status to 7.43 for CYP2E1 c1/c1 with slow acetylator status. After adjustment for acetylator status and age, the CYP2E1 c1/c1 genotype remained an independent risk factor for hepatotoxicity (OR, 2.38; P =.017). Furthermore, under the administration of isoniazid, the volunteers with CYP2E1 c1/c1 genotype had higher CYP2E1 activity than those with other genotypes had and, hence, might produce more hepatotoxins. In conclusion, CYP 2E1 genetic polymorphism may be associated with susceptibility to antituberculosis drug-induced hepatitis.     

Genetic polymorphisms of NAT2 and CYP2E1 associated with antituberculosis drug-induced hepatotoxicity in Korean patients with pulmonary tuberculosis

Antituberculosis drug-induced hepatitis attributed to isoniazid (INH) is one of the most prevalent drug-induced liver injuries. INH is metabolized by hepatic N-acetyltransferase (NAT) and cytochrome P450 2E1 (CYP2E1) to form hepatotoxins. The aim of this study was to evaluate whether polymorphisms of the NAT2 and/or CYP2E1 genes were associated with antituberculosis drug-induced hepatotoxicity in Korean patients. A total of 132 patients with tuberculosis who received antituberculosis treatment were followed prospectively. Their NAT2 and CYP2E1 genotypes were determined using polymerase chain reaction (PCR) with or without sequencing. Eighteen (13.6%) patients developed antituberculosis drug-induced hepatotoxicity. Regarding NAT2, slow acetylators had a higher incidence of hepatotoxicity than rapid acetylators (36.8% vs. 9.7%, P=0.005) and there was a 3.8-fold risk of hepatotoxicity for the slow acetylators compared to the rapid acetylators. For the CYP2E1 gene, the RsaI polymorphism in the 5' untranslated region, and a polymorphic repetitive sequence at the CYP2E1 5'-flaking region were analyzed; there was no significant association between any CYP2E1 genotype and antituberculosis drug-induced hepatotoxicity. In conclusion, slow acetylator status of NAT2 was a significant susceptibility risk factor for antituberculosis drug-induced hepatotoxicity; NAT2 genotyping may be a useful tool for predicting antituberculosis drug-induced hepatotoxicity.     

CYP2E1 Pst Ⅰ/Rsa Ⅰ polymorphism and colorectal cancer risk:A meta-analysis

AIM:To clarify the association between CYP2E1 PstⅠ/RsaⅠ polymorphism and susceptibility to colorectal cancer.METHODS:A meta-analysis based on 10 eligible casecontrol studies involving 4979 cases and 6012 controls was carried out to summarize the data on the association between CYP2E1 RsaⅠ/PstⅠ polymorphism and colorectal cancer risk.RESULTS:In comparison of the homozygote c2c2 and c2 carriers(c1c2 + c2c2) and the homozygous wild-type genotype(c1c1),no association was found between CYP2E1 RsaⅠ/PstⅠ polymorph...     

CYP2E1 PstI/RsaI polymorphism and colorectal cancer risk: A meta-analysis

AIM: To clarify the association between CYP2E1 PstI/RsaI polymorphism and susceptibility to colorectal cancer.METHODS: A meta-analysis based on 10 eligible case-control studies involving 4979 cases and 6012 controls was carried out to summarize the data on the association between CYP2E1 RsaI/PstI polymorphism and colorectal cancer risk.RESULTS: In comparison of the homozygote c2c2 and c2 carriers (c1c2 + c2c2) and the homozygous wild-type genotype (c1c1), no association was found between CYP2E1 RsaI/PstI polymorphism and colorectal cancer risk [odds ratio (OR) = 1.24 (95% CI: 0.93-1.66) for c2c2; OR = 1.02 (95% CI: 0.88-1.19) for c2 carriers]. In stratified analysis, Caucasians with c2c2 homozygote appeared to have an increased risk of colorectal cancer (OR = 2.67, 95% CI: 1.03-6.89, P = 0.043), no significant associations were found in other groups.CONCLUSION: c2c2 homozygote of CYP2E1 PstI/RsaI polymorphism may be associated with the increased risk of colorectal cancer in Caucasians, which needs further investigations.     

NAT2 genetic polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in Chinese community population

Background. Anti-tuberculosis drug-induced hepatotoxicity (ATDH) is one of the most prevalent and serious adverse drug reactions in the course of anti-tuberculosis (TB) treatment. Some researchers suggested that determination of N-acetyltransferase 2 (NAT2) genotype may be clinically useful to identify patients at high risk of developing ATDH. Aim. To evaluate whether the NAT2 genotype could be as a predictor for ATDH in Chinese community TB population. Material and methods. A total of 4304 community-based TB patients were followed up six to nine months prospectively. A nested case-control study was designed. Each ATDH case was 1:4 matched with controls by age (within 5 years old), gender, treatment history, disease severity and drug dosage. The polymorphisms of NAT2 were determined using polymerase chain reaction with restriction fragment length polymorphism. Conditional Logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI), as well as corresponding P-values. Results. A total of 89 ATDH cases and 356 controls were included in this study. Allele frequency of NAT2*5, NAT2*6 and NAT2*7 in cases and controls were 4.5 and 3.2%, 25.3 and 26.5%, and 13.5 and 13.5%, respectively. Frequencies of genotypes and alleles of NAT2*5, NAT2*6 and NAT2*7 did not differ significantly between cases and controls. The OR of intermediate acetylator and slow acetylator compared with rapid acetylator was 1.040 (95%CI 0.616-1.758) and 0.990 (95%CI 0.509-1.925), respectively. The NAT2 haplotype distribution in cases was similar to controls. Conclusions. In conclusion, we did not find significant association between NAT2 genotype and ATDH in community-based Chinese population. It may be deficient to take NAT2 genotype as a predictor for ATDH in Chinese community TB patients.     

Polymorphism of the N-acetyltransferase 2 gene as a susceptibility risk factor for antituberculosis drug-induced hepatitis

Antituberculosis drug-induced hepatitis is one of the most prevalent drug-induced liver injuries. Isoniazid is the major drug incriminated in this hepatotoxicity. Isoniazid is mainly metabolized to hepatotoxic intermediates by N-acetyltransferase (NAT). However, the association of polymorphic NAT acetylator status and antituberculosis drug-induced hepatitis is debatable. To determine whether acetylator status is a risk factor for antituberculosis drug-induced hepatitis, we genotyped NAT2 in 224 incident tuberculosis patients who received antituberculosis treatment. Antituberculosis drug-induced hepatitis was diagnosed based on a positive isoniazid rechallenge test and exclusion of viral hepatitis. Acetylator status was determined by genotyping NAT2 in patients using a polymerase chain reaction with restriction fragment length polymorphism. Univariate analysis and logistic regression analysis were used to evaluate the risk factors of isoniazid-induced hepatitis. Thirty-three patients (14.7%) were diagnosed with antituberculosis drug-induced hepatitis. Slow acetylators had a higher risk of hepatotoxicity than rapid acetylators (26.4% vs. 11.1%, P =.013). Among patients with hepatotoxicity, slow acetylators had significantly higher serum aminotransferase levels than rapid acetylators. Logistic regression showed that slow-acetylator status (odds ratio [OR], 3.66; 95% CI, 1.58-8.49; P =.003) and age (OR, 1.09; 95% CI, 1.04-1.14; P <.001) were the only 2 independent risk factors for antituberculosis drug-induced hepatitis. In conclusion, slow-acetylator status of NAT2 is a significant susceptibility risk factor for antituberculosis drug-induced hepatitis. Additionally, slow acetylators are prone to develop more severe hepatotoxicity than rapid acetylators. Regular monitoring of serum aminotransferase levels is mandatory in patients receiving antituberculosis treatment, especially in slow acetylators.     

Drug-metabolising enzyme polymorphisms and predisposition to anti-tuberculosis drug-induced liver injury: a meta-analysis

BACKGROUND: Although some case-control studies have investigated the association between drug-metabolising enzyme (DME) gene polymorphisms and susceptibility to anti-tuberculosis drug-induced liver injury (ATLI), their results are conflicting, mainly due to limited power. OBJECTIVE: To review the literature systematically, by means of a meta-analytical review, to evaluate the putative association and provide a quantitative summary estimate on the association with ATLI. DESIGN: We searched the databases of MEDLINE, PubMed, EMBASE and CBMdisc from 1966 to May 2007 using 'DME', 'hepatotoxicity', 'genetic polymorphism', 'genetic susceptibility' in combination with 'antitubercular agents', performed a manual search of citations from relevant original studies and review articles, and corresponded with authors. RESULTS: Nine eligible articles were included in this meta-analysis, including five on N-acetyltransferase 2 (NAT2), four on cytochrome P450 2E1 (CYP2E1) and two on glutathione S-transferase (GST) studies, separately. The overall ORs of ATLI risk associated with NAT2 homozygous variant genotype (mt/mt), CYP2E1 homozygous wild genotype (*1A/*1A), GSTM1 homozygous null genotype (null/null) and GSTT1 homozygous null genotype (null/null) were respectively 1.93 (95%CI 0.81-4.62), 2.22 (95%CI 1.06-4.66), 2.62 (95%CI 1.45-4.75) and 1.18 (95%CI 0.61-2.29). In addition, the OR for Asian ATLI associated with the NAT2 homozygous variant (mt/mt) and the combined genotype (w/w + w/mt) was 2.52 (95%CI 1.49-4.26). CONCLUSIONS: NAT2 mt/mt, CYP2E1*1A/*1A and GSTM1 null/null were observed to increase the risk of ATLI in tuberculosis patients. Our results support the hypothesis that NAT2 mt, CYP2E1*1A and GSTM1 null have a modest effect on genetic susceptibility to ATLI, but no significant evidence for GSTT1 null/null.     

CYP2E1 Rsa Ⅰ polymorphism impacts on risk of colorectal cancer association with smoking and alcohol drinking

AIM： To investigate associations between the Rsa I polymorphism of CYP2E1 and risk of colorectal cancer. METHODS： A case-control study was conducted with 315 colorectal cancer cases （105 colon, 210 rectal） and 439 population-based controls in Jiangsu Province of China. Genomic DNA samples were assayed for restriction fragment length polymorphisms in CYP2E1 by PCR amplification followed by digestion with Rsa I. Information on smoking and alcohol drinking was collected using a questionnaire. Odds ratios （ORs） were estimated with an unconditional logistic model. RESULTS： The proportional distribution of the CYP2E1 Rsa I c1/c1, c1/c2 and c2/c2 genotypes were 61.4%, 35.6% and 3.0% in controls, 60.6%, 33.7% and 5.8% in colon cancer cases, and 58.4%, 34.0% and 7.7% in rectal cancer cases, respectively. A significant differencewas noted between controls and rectal cancer cases （P = 0.029）, the c2/c2 genotype being associated with elevated OR （adjusted age, sex and status of the smoking and alcohol drinking） for rectal cancer （1.64, 95% CI, 1.12-2.41, vs cl allele carriers）, but not for colon cancer. In interaction analysis between the CYP2E1 Rsa I genotype and smoking and drinking habits, we found a significant cooperative action between the c2/c2 genotype and alcohol drinking in the sex-, age-adjusted ORs for both colon （4.74, 95% CI, 1.10-20.40） and rectal （5.75, 95% CI, 1.65-20.05） cancers. Among nonsmokers, the CYP2E1 Rsa I c2/c2 genotype was also associated with elevated ORs in the two sites （1.95, 95% CI, 0.99-3.86 and 2.30, 95% CI, 1.32-3.99）. CONCLUSION： The results of the present study suggest that the CYP2E1 c2/c2 genotype increases susceptibility to rectal cancer and the gene-environmental interactions between the CYP2E1 polymorphism and smoking or alcohol drinking exist for colorectal neoplasia in general.     

CYP2E1 Rsa Ⅰ polymorphism impacts on risk of colorectal cancer association with smoking and alcohol drinking

AIM: To investigate associations between the Rsa Ⅰpolymorphism of CYP2E1 and risk of colorectal cancer.METHODS: A case-control study was conducted with 315 colorectal cancer cases (105 colon, 210 rectal)and 439 population-based controls in Jiangsu Province of China. Genomic DNA samples were assayed for restriction fragment length polymorphisms in CYP2E1by PCR amplification followed by digestion with Rsa Ⅰ. Information on smoking and alcohol drinking was collected using a questionnaire. Odds ratios (ORs) were estimated with an unconditional logistic model.RESULTS: The proportional distribution of the CYP2E1 Rsa Ⅰ c1/c1, c1/c2 and c2/c2 genotypes were 61.4%,35.6% and 3.0% in controls, 60.6%, 33.7% and 5.8%in colon cancer cases, and 58.4%, 34.0% and 7.7% in rectal cancer cases, respectively. A significant difference was noted between controls and rectal cancer cases (P = 0.029), the c2/c2 genotype being associated with elevated OR (adjusted age, sex and status of the smoking and alcohol drinking) for rectal cancer (1.64,95% CI, 1.12-2.41, vs c1 allele carriers), but not for colon cancer. In interaction analysis between the CYP2E1Rsa Ⅰ genotype and smoking and drinking habits, we found a significant cooperative action between the c2/c2 genotype and alcohol drinking in the sex-, age-adjusted ORs for both colon (4.74, 95% CI, 1.10-20.40) and rectal (5.75, 95% CI, 1.65-20.05) cancers. Among nonsmokers, the CYP2E1 Rsa Ⅰ c2/c2 genotype was also associated with elevated ORs in the two sites (1.95, 95%CI, 0.99-3.86 and 2.30, 95% CI, 1.32-3.99).CONCLUSION: The results of the present study suggest that the CYP2E1 c2/c2 genotype increases susceptibility to rectal cancer and the gene-environmental interactions between the CYP2E1 polymorphism and smoking or alcohol drinking exist for colorectal neoplasia in general.     

Role of polymorphic N-acetyl transferase2 and cytochrome P4502E1 gene in antituberculosis treatment-induced hepatitis

Background and Aim: Antituberculosis drugs, isoniazid and rifampicin, in combination, are known to develop drug‐induced hepatotoxicity (DIH). A higher risk of DIH during antituberculosis treatment (ATT) has been reported in the Indian subcontinent compared to its Western counterparts. The role of genetic factors in a higher incidence of ATT hepatotoxicity in the Indian population is still unclear. The present study was aimed at investigating the role of the N‐acetyltransferase2 (NAT2) and cytochrome P4502E1 (CYP2E1) gene polymorphisms in ATT hepatotoxicity. Methods: The study population included 218 pulmonary tuberculosis patients who were started on ATT and followed up for the occurrence of ATT‐induced hepatitis. The genetic polymorphisms of the NAT2 and CYP2E1 genes were studied by polymerase chain reaction–restriction fragment length polymorphism. Results: The occurrence of DIH was 18.8% (41/218). There was a higher prevalence of NAT2 slow‐acetylator genotypes in DIH (70.73%) compared to non‐DIH (44.63%; P < 0.05). The frequency of the NAT2*5/*7 and NAT2*6/*7 genotypes was significantly higher in DIH than non‐DIH (19.51% vs 6.78%, and 19.51% vs 5.08%). No association of the CYP2E1 RsaI polymorphism could be demonstrated with DIH. However, the DraI C/D genotype of the CYP2E1 gene was mostly prevalent in DIH (85.37%), compared to non‐DIH (64.41%) (P < 0.05). Slow‐acetylator status and the CYP2E1 C/D or C/C genotype together showed a higher frequency in DIH (65.85%) compared to non‐DIH (28.81%) (P < 0.0001). Conclusion: The study demonstrates for the first time a possible association between the DraI polymorphism of the CYP2E1 gene and the risk of ATT hepatotoxicity. The genotyping of the NAT2 and CYP2E1 genes could possibly identify the groups at highest risk of developing ATT‐induced hepatitis prior to medication.