Cytochrome P450 2E1 Gene Polymorphism Research Articles

Relationship between Cytochrome P450 2E1 Gene Polymorphism and Susceptibility of Low Birth Weight Infants

ABSTRACT The purpose of this study is to investigate the relationship between cytochrome P450 2E1 (CYP2E1) RsaI/PstI and DraI single gene polymorphism (SNP) and low birth weight infants (LBW) of Chinese population. The researchers detected CYP2E1 RsaI/PstI and DraI SNPs by real-time PCR cycling and HRM analysis in 461 premature delivery and 461 healthy pregnant women. This paper found that RsaI/PstI C2C2 was statistically significantly correlation with increased risk of LBW (Odds ratios= 0.66,95% CI: 0.44–0.98, P = 0.04) and (Odds ratios = 0.75 , 95% CI: 0.56–0.99, P=0.04) for C2C2, compared with C1C1 and C1C1 + C1C2, respectively. When CYP2E1 RsaI/PstI and DraI SNPs combine, the risk of low birth weight infants was increased in individuals with both DraI TT and RsaI/ PstI C2C2 genotypes (Odds ratios=0.59, 95% CI=0.36–0.97). The current study demonstrates CYP2E1 RsaI/PstI polymorphism is significantly related to LBW and the interaction between the RsaI/PstI and DraI polymorphisms has a significant impact on LBW.

Genetic polymorphism of the drug-metabolizing enzyme Cytochrome P4502E1 (CYP2E1) in a healthy Saudi population

ObjectivesCytochrome P450 2E1 (CYP2E1) is one of the major enzymes involved in the metabolism and detoxification of various drugs and xenobiotics. Polymorphisms in the CYP2E1 gene exhibit high inter-individual variations associated with alterations in CYP2E1 gene expression and enzyme function. This study aimed to determine the genotype distributions and allele frequencies of CYP2E1*1B, *5B, and *6 polymorphisms among Saudis in western Saudi Arabia. MethodsIn total, 140 healthy Saudis attending King Abdulaziz University Hospital between February and April 2021 were included in the study. CYP2E1 gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. ResultsThe genotype frequencies of CYP2E1*1B A2A2, A2A1, and A1A1 were 54.29%, 40%, and 8%, respectively. The frequencies of CYP2E1*5B c1c1 and c1c2 genotypes were approximately 99.93% and 0.07%, respectively. The frequencies of the CYP2E1*6 DD, DC, and CC genotypes were 91.43%, 7.85%, and 0.72%, respectively. The genotype distributions for these polymorphisms were consistent with the expected distribution based on Hardy-Weinberg equilibrium. The allele frequencies were 74.29% A2 and 25.71% A1 for CYP2E1*1B, 99.64% c1 and 0.36% c2 for CYP2E1*5B, and 95.36% D and 4.65% C for CYP2E1*6. ConclusionThe genotype distribution of CYP2E1*1B polymorphism was higher in the western Saudi population, whereas the CYP2E1*5B and *6 polymorphisms were lower than the global average. Knowledge of the prevalence of CYP2E1 polymorphisms among our population will provide a better understanding of whether individual patients might benefit from their medication or whether they might develop adverse effects.

Cytochrome P450 2E1 gene polymorphism and alcohol drinking on the risk of hepatocellular carcinoma: a meta-analysis.

The gene polymorphism of Cytochrome P450 2E1 (CYP2E1) is supposed to be associated with cancer susceptibility. Many studies focusing on the Pst I/Rsa I polymorphism of CYP2E1 gene and hepatocellular carcinoma (HCC) risk have been conducted and the results are conflicting. In the current study, a meta-analysis of published studies was performed to assess the association between CYP2E1 Pst I/Rsa I polymorphism and risk to HCC. 11 studies containing 1,178 cases and 1,623 controls were selected to determine whether c2 allele of CYP2E1 gene can increase HCC susceptibility, especially through interacting with alcohol drinking. Using the random effects model, the result indicated that there was no association between CYP2E1 Pst I/Rsa I genotype and HCC risk [odds ratio (OR) 1.03 (95% confidence interval (CI): 0.76-1.40) for c2 variant allele and OR 0.82 (95% CI: 0.51-1.31) for c2 homozygotes compared with wild-type homozygotes]. The association between CYP2E1 (c2) variant allele and HCC susceptibility were found when interacting with alcohol [OR 2.88 (95% CI: 1.25-6.60)]. In conclusion, this meta-analysis results showed that Pst I/Rsa I polymorphism of CYP2E1may slightly increase the risk of HCC and alcohol consumption increases the probability of developing HCC, especially for the carriers of some CYP2E1 alleles. CYP2E1 Pst I/Rsa I polymorphism may contribute to the proportion cases of HCC, which needs further investigations.

N-acetyltransferase 2, cytochrome P4502E1 and glutathione S-transferase genotypes in antitubercular treatment-induced hepatotoxicity in North Indians

Tuberculosis (TB) is a major cause of illness and death in developing countries. Hepatotoxicity is a serious side effect of antituberculosis treatment (ATT). NAT2, CYP2E1 and glutathione S-transferase (GST) gene polymorphisms may play an important role in ATT-induced hepatotoxicity. So, elucidating the genetics involved in anti-TB drug-induced hepatotoxicity in patients would be of utmost clinical significance. Therefore, the objective of the study was to elucidate the role of NAT2, CYP2E1 and GST gene polymorphisms in ATT-induced hepatotoxicity in North Indian patients. Three hundred patients with pulmonary and extra-pulmonary TB were enrolled. Total genomic DNA was isolated from each patient's peripheral lymphocytes using phenol-chloroform method, and genetic polymorphic analysis for N-acetyltransferase 2 (NAT2), cytochrome P4502E1 (CYP2E1) and GST was performed by polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP). Of the 300 patients, 185 were males and 115 females. Among them, 33 males and 22 females developed ATT-induced hepatotoxicity. There were significant increases in alanine aminotransferase, aspartate aminotransferase and bilirubin levels in patients with ATT-induced hepatotoxicity at 1month of treatment. NAT2 5/7 and 6/7 were significantly higher in hepatotoxicity patients as compared to the non-hepatotoxicity group. c1/c1 allele of CYP2E1 gene was lower (50·9%) in ATT-induced hepatotoxicity patients as compared to non-hepatotoxicity patients (61·2%), whereas c1/c2 and c2/c2 alleles were higher, but not statistically significant. GSTM1 was significantly higher in hepatotoxicity patients as compared to non-hepatotoxicity patients, whereas GSTT1 and GSTT1/M1 were lower, but not statistically significant. This study indicates that patients with slow-acetylator genotypes (NAT2 5/7, 6/7) and GSTM1 allele of GST enzyme were at higher risk of ATT-induced hepatotoxicity.

Association of cytochrome P450 2E1 gene polymorphism and the risk of small-cell lung cancer

小细胞肺癌在肺癌中恶性度极高.细胞色素P450 2El基因(CYP2E1)作为一种重要的Ⅰ相代谢酶参与多种致癌物的代谢,其位点多态性可影响自身表达[1].本研究采用病例对照研究方法,分析CYP2E 1-1239位点多态性与小细胞肺癌发病风险的关系.1.对象与方法:(1)研究对象:唐山工人医院和唐山市人民医院自2008年3月至2012年12月经病理确诊的203例小细胞肺癌患者.406例对照为唐山地区健康体检个体,无既往肿瘤史和体征,按年龄和性别与病例组1:2频数匹配.所有研究对象均获知情同意,并捐献2 ml静脉血用于基因组DNA提取. 关键词：小细胞肺癌;细胞色素P450 2E1基因;单核苷酸多态性

CYP2E1 Gene Promoter Polymorphism -1293G>C Increases the Risk of Essential Hypertension in Men with Alcohol Abuse

We studied the association between of cytochrome P450 2E1 (CYP2E1) gene polymorphism and risk of essential hypertension development depending on alcohol drinking habit in unrelated men in Russian population (patients with essential hypertension and healthy volunteers). All participants were genotyped for four CYP2E1 gene polymorphisms -1293G>C (rs3813867), -1053C>T (rs2031920), 7632T>A (rs6413432), and 9896C>G (rs2070676) by PCR and restriction analysis. We found statistically significant associations between -1293C allele (OR=5.04, 95% CI=1.23-20.70, p=0.03) and -1293GC genotype (OR=5.36, 95% CI=1.28-22.50, p=0.03) with increased risk of essential hypertension in men. Stratified analysis on alcohol drinking habit showed that the presence of -1293C allele (OR=6.82, 95% CI=1.12-41.70, p=0.04) and -1293GC genotype (OR=7.61, 95% CI=1.2-48.4, p=0.03) in men with alcohol abuse increases the risk of essential hypertension. The obtained data suggest that excessive alcohol consumption and increased induction of cytochrome in the carriers of -1293C allele of CYP2E1 gene lead to generation of highly reactive free radical oxidation products. These processes induced oxidative stress and endothelial induction, which served as the pathogenetic basis for essential hypertension.

Roles of Cytochrome P4502E1 Gene Polymorphisms and the Risks of Alcoholic Liver Disease: A Meta-Analysis

BackgroundPrevious studies investigating the association between cytochrome P4502E1 (CYP2E1) polymorphisms and the risk of alcoholic liver diseases (ALD) have yielded conflicting results. Thus, a meta-analysis was performed to clarify the association between CYP2E1 polymorphisms and the risks of ALD.MethodsA comprehensive literature search was conducted to identify the relevant studies. The fixed or random effect model was selected based on the heterogeneity test among studies. Publication bias was estimated using Begg’s funnel plots and Egger’s regression test.ResultsA total of 27 and 9 studies were finally included for the association between the CYP2E1 Pst I/Rsa I or Dra I polymorphisms and the risks of ALD, respectively. Overall, the combined results showed that homozygous genotype c2c2 was significantly associated with increase risk of ALD in worldwide populations (c2c2 vs. c1c1: OR = 3.12, 95%CI 1.91–5.11) when ALD patients were compared with alcoholics without ALD. Significant associations between CYP2E1 Pst I/Rsa I polymorphism and ALD risk were also observed in Asians (c2c2 vs. c1c1: OR = 4.11, 95%CI 2.32–7.29) and in Caucasians (c2c2/c1c2 vs. c1c1: OR = 1.58, 95%CI 1.04–2.42) when ALD patients were compared with alcoholics without ALD. However, subgroup analysis stratified by ALD types showed that CYP2E1 Pst I/Rsa I polymorphism was not significantly associated with the risks of alcoholic cirrhosis (ALC). No significant association was observed between CYP2E1 Dra I polymorphism and ALD risks.ConclusionThis meta-analysis suggested that CYP2E1 Pst I/Rsa I polymorphism might be not significantly associated with advanced form of ALD (ALC), but might be significantly associated with other form of ALD such as steatosis, hepatisis, fibrosis. Furthermore, CYP2E1 Dra I polymorphism might be not significantly associated with the ALD risks. Since potential confounders could not be ruled out completely, further studies were needed to confirm these results.

Effect of Different Doses of Wheatgrass in Prevention of Carbon Tetrachloride Induced Hepatotoxicity in Rats

© 2011, INASL 39 HEPATOTOXICITY Effect of Different Doses of Wheatgrass in Prevention of Carbon Tetrachloride Induced Hepatotoxicity in Rats JK Kamboj*, SV Rana*, DK Dhawan**, K Vahiphei*** Departments of *Gastroenterology and **Pathology, PGIMER, Chandigarh, ***Department of Biophysics, Punjab University, Chandigarh Introduction: Wheatgrass (Triticum aestivum), rich in chlorophyll and various antioxidants, is promoted to treat a number of conditions including common cold, cough, fever, eczema and burns, etc. Aim: To determine the protective effect of different doses of wheatgrass in hepatic tissue of Wistar rats damaged by CCl4. Material and Methods: Wheatgrass was administered orally at different doses of 20 mg, 40 mg, 60 mg and 80 mg/100 g by body weight in drinking water for 4 weeks along with CCl4 injection given subcutaneously at a dose of 2 mL/Kg body weight twice a week. Wheatgrass dose was started 2 weeks prior to first injection of CCl4. Carbon tetrachloride was also administered in control group for 4 weeks and one group was given only wheatgrass at a maximum dose of 80 mg/100 g by body weight/day to check any adverse effect of wheatgrass on liver. The effect to different treatments was studied on serum enzymes like alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rats at different time intervals of 2 and 4 weeks and the rat liver was analyzed histologically at the end of study. Results: Serum ALP, AST, ALT activity was significantly increased when estimated at the intervals of 2 and 4 weeks as compared to baseline values in CCl4 group. Interestingly, supplementation of wheatgrass to rats helped in regulating the altered activities of ALP, AST and ALT in serum at 4 weeks. However, wheatgrass treatment to rats did not indicate any significant change in the activities of all abovementioned liver enzymes at the interval of 2 weeks. Histologically, there was necrosis, portal triaditis and lobular inflammation in CCl4 group. Maximum protection was observed biochemically and histologically with wheatgrass dose of 80 mg/100 g body weight Conclusion: Carbon tetrachloride caused liver toxicity and wheatgrass treatment prevented the increase in liver enzymes and histology depending on the dose of wheatgrass. Conflict of Interest: None Relation of NAT2, CYP2E1 and GST Gene Polymorphisms with Anti-tuberculosis Treatment Induced Hepatotoxicity in North Indian Patients SV Rana*, SK Sharma**, RP Ola*, SK Arora***, SK Sinha*, JK Kamboj*, K Singh* Department of Superspecialty of *Gastroenterology, **Biophysics and ***Immunopathology, PGIMER, Chandigarh Background: Antituberculosis treatment (ATT) induced hepatitis is attributed to isoniazid (INH). Isoniazid is metabolized by hepatic N-acetyltransferase-2 (NAT-2) and cytochrome P-450 2E1 (CYP2E1) to form hepatotoxins. Glutathione-S-transferase (GST) plays an important role in prevention of ATT-induced hepatotoxicity. Deficiency of GST activity because of homozygous null mutations at GSTM1 and GSTT1 loci may modulate susceptibility to ATT-induced hepatotoxicity. Aim: To evaluate whether polymorphisms of NAT-2, GST and CYP2E1 gene were associated with ATT-induced hepatotoxicity in North Indian patients. Methods: In this prospective study, 250 patients treated with ATT for tuberculosis were genotyped for polymorphisms of NAT-2, GST and CYP2E1. NAT-2, CYP2E1 and GST genotypes were determined by PCR and multiplex PCR with restriction fragment length polymorphism analysis (RFLP). Results: Two hundred fifty tuberculosis (TB) patients on ATT (153 males) were studied. Out of 250 patients, 32 (12.8%) developed hepatotoxicity. NAT-2 gene allele 4/4 was present in 18/32 (56.2%) of hepatotoxicity patients while in 76/218 (34.8%) in non-hepatotoxicity patients. Allele 4/6, 5/5, 6/6 and 7/7 were not present in hepatotoxicity patients while these were present in non-hepatotoxicity patients. In GST, out of 32 hepatotoxicity patients, 5 (15.6%) showed GSTM1, 9 out of 32 (28.0%) GSTT1 and 18 out of 32 (56.3%) GSTT1/ GSTM1/s-globulin. While 69 out of 218 (31.7%) showed GSTM1, 34 (15.6%) GSTT1, and 115 (52.7%) GSTT1/GSTM1/s-globulin in nonhepatotoxicity patients. For CYP2E1 c1/c1, c2/c2 and c1/c2 genotypes in INH-NH patients were 61.1%, 16.6% and 22.2% respectively while in INH-H patients 50.0%, 25.0% and 25.0% respectively. Conclusion: This study suggests that NAT-2 gene allele 4/4 was significantly higher in INH-induced hepatotoxicity as compared to nonhepatotoxicity group. There was no significant difference in CYP2E1 and GST genotypes between both the groups. Conflict of Interest: None 03_JCEH-Abstract.indd 39 3/18/2011 11:13:05 AM

Meta-analyses of the effect of cytochrome P450 2E1 gene polymorphism on the risk of head and neck cancer

Many studies have investigated the association between the CYP2E1 5'-flanking region (RsaI/PstI) polymorphism and head and neck cancer susceptibility, but the results were conflicting. In this meta-analysis, we assessed 24 published studies involving 12,562 subjects of the association between CYP2E1 RsaI/PstI polymorphism and head and neck cancer risk. Using the fixed effects model, we found significant association between PstI/RsaI polymorphism and head and neck cancer risk [OR=1.11 (95%CI: 1.00-1.22) for c2 allele (P=0.04) and OR=1.57 (95% CI: 1.14-2.15) for c2 homozygous (P=0.006) compared with wild type homozygote]. Significant results were also found in East Asians and Mix populations when stratified by ethnicity. However, no significant associations were found for Caucasians in all genetic models. Stratified analyses according to source of controls, significant associations were found only in hospital base controls. In the subgroup analyses by tumor types, significant association was detected only in oral cancer group, while no significant associations among laryngeal- or pharyngeal- cancer subgroup. This meta-analysis suggests that the CYP2E1 RsaI/PstI polymorphism may be a risk factor for head and neck cancer in Asians and Mix population, and that different carcinogenic processes involved in the genesis of various tumor types may exist.

Role of CYP2E1 gene polymorphisms association with hepatitis risk in Northeast India.

To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India. A total of 104 jaundice patients and 124 community controls were included. Serological analysis was performed by routine enzyme-linked immunosorbent assay, and nucleic acid testing for hepatitis viruses was done by polymerase chain reaction (PCR), followed by PCR direct sequencing for viral genotyping. Cytochrome P450 2E1 (CYP2E1) polymorphism was studied by PCR-restriction fragment length polymorphism. Nitrite and volatile nitrosamines in indigenous foods consumed routinely by the Northeast Indian ethnic population were estimated by Griess's reagent and GC-MS, respectively. Hepatitis A virus (HAV) infection was predominantly prevalent (36.5%) in our cohort, followed by hepatitis B virus (HBV), hepatitis E virus (HEV) and hepatitis C virus. HBV genotype D and HEV genotype 1 were the most dominant. CYP2E1 c1/c2 genotype frequency was comparatively higher in alcoholic (P < 0.0001, OR = 30.5) and cryptogenic (P = 0.014, OR = 8.714) patients, and was associated with significantly higher hepatitis risk (P = 0.0.007, OR = 6.489). Mutant C allele of Cyp2E1 DraI frequency was comparatively higher in HAV (P = 0.006), alcoholic (P = 0.003) and cryptogenic (P = 0.014) cases, and was associated with overall hepatitis risk (P = 0.026, OR = 5.083). Indigenous foods, Gundruk, Kharoli, betel leaf and nuts were found to have the highest nitrite content. Apart from viral factors, CYP2E1 polymorphism might be associated with increased risk of liver diseases in Northeast India. Indigenous foods that contain nitrite and nitrosamine might be an associated risk factor.

Association of combined CYP2E1 gene polymorphism with the risk for esophageal squamous cell carcinoma in Huaiʼan population, China

Cytochrome P450 2E1 (CYP2E1) has an important role in the metabolic activation of precarcinogens such as N-nitrosoamines and other low relative molecular mass, organic compounds. This study examined whether CYP2E1 RsaI and DraI polymorphism are associated with susceptibility to esophageal squamous cell carcinoma and the correlation between the genotypes and expression levels of CYP2E1 mRNA. Seventy-seven patients with newly diagnosed, untreated esophageal squamous cell carcinoma and 79 healthy controls matched in age, gender and residence were recruited for the control study. An RsaI polymorphism in the 5'-flanking region and a DraI polymorphism in the sixth intron of the CYP2E1 gene, which could possibly affect its transcription, were determined in this study by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and mRNA level of CYP2E1 was measured by quantitative real-time reverse transcription PCR. No significant association of RsaI or DraI polymorphism of CYP2E1 with susceptibility of esophageal squamous cell carcinoma were demonstrated (OR = 1.67, 95% CI: 0.89 - 3.15, P = 0.11; OR = 1.11, 95% CI: 0.59 - 2.09, P = 0.74, respectively). With SHEsis software, no linkage disequilibrium was detected between RsaI and DraI polymorphism (D' = 0.528, r(2) = 0.27). When combined RsaI polymorphism with DraI polymorphism, the association between that carrying c2 allele and DD genotype and the risk for esophageal squamous cell carcinoma were found (OR = 5.77, 95% CI: 1.65 - 20.22). Compared with the normal controls, the mRNA levels with RsaI polymorphism, DraI polymorphism, or any combined genotypes in cases showed no statistical difference. This study suggests that carrying c2 allele and DD genotype conferreded an elevated risk for esophageal squamous cell carcinoma. There was no significant statistical relationship between the genotypes c1/c2, D/C, or the combined allele and mRNA expression.

A polymorphism in the 5'-flanking region of the CYP2E1 gene and elevated lung adenocarcinoma risk in a Japanese population

Cytochrome P450 2E1 (CYP2E1) catalyzes the metabolic activation of the procarcinogen, N-nitrosodimethylamine, and cytotoxic carbon tetrachloride compounds. A tandem repeat polymorphism in the 5'-flanking region of the CYP2E1 gene was investigated in non-small cell lung carcinoma (NSCLC) patients to clarify the relationship between CYP2E1 gene polymorphism and lung cancer susceptibility. Blood samples were taken from 236 healthy control subjects (192 males and 44 females) and 111 patients (78 males and 33 females) who underwent surgery for NSCLC in Japan. DNA was isolated from these samples and the 5'-flanking region of the CYP2E1 gene was amplified by polymerase chain reaction and examined for tandem repeat polymorphisms using DNA fragment analysis. Sequence analysis confirmed the presence of three alleles, A2, A3, and A4 (361, 367, and 457 bp, respectively), with four genotypes observed in the lung cancer group and five genotypes in the control group. There was a statistically significant difference in genotype distribution between the lung adenocarcinoma and control group (P=0.0088, A4/A4 vs. non-A4/A4). In the lung adenocarcinoma group, the univariate risk estimates for the A4/A4 subgroup compared to the most common subgroup (A2/A2) was 4.300 (95% confidence interval = 1.358-13.618, P=0.0131). We conclude that the A4/A4 genotype of the 5'-flanking region of CYP2E1 was significantly more frequent in lung adenocarcinoma cases than in healthy controls and, therefore, may be involved in the development of lung adenocarcinoma.

Gene–environmental interactions between alcohol-drinking behavior and ALDH2 and CYP2E1 polymorphisms and their impact on micronuclei frequency in human lymphocytes

Ethanol is converted to acetaldehyde by alcohol dehydrogenase (ADH), cytochrome p4502E1 (CYP2E1) and catalase. This metabolite is then detoxified by aldehyde dehydrogenase 2 (ALDH2), a key enzyme in the elimination of acetaldehyde, via further oxidation to acetic acid. The toxic effects of acetaldehyde are well documented and may be partially mediated by genotoxic damage. In the present study, we investigated the effects of alcohol-drinking behavior and genetic polymorphisms in two different genes (ALDH2 and CYP2E1) on the micronuclei (MN) frequency in 248 healthy Japanese men. Genotyping was performed by PCR–RFLP analysis. The ALDH2 variant (deficient type) was significantly associated with an increased MN frequency in subjects drinking more than three times/wk, while habitual drinkers with wild-type CYP2E1 also had a significantly increased MN frequency. Furthermore, when the subjects were divided into eight groups according to their drinking frequency and genotypes of ALDH2 and CYP2E1, we found that habitual drinkers with homozygous CYP2E1 *1/ *1 and heterozygous ALDH2 *1/ *2 or homozygous ALDH2 *2/ *2 showed the highest mean MN frequency. In the present study, we found clear associations among ALDH2 and CYP2E1 gene polymorphisms, alcohol-drinking behavior and genotoxic effects in a healthy Japanese population. Therefore, analysis of the polymorphisms of alcohol-metabolizing enzymes may lead to elucidation of the mechanism(s) for individual susceptibilities to the toxicity of ethanol metabolites.

Hepatitis B and C viruses infection, lifestyle and genetic polymorphisms as risk factors for hepatocellular carcinoma in Haimen, China.

A case‐control study was carried out to investigate the impact of factors including virus infection, aflatoxin B1, microcystins, smoking/drinking and dietary habits as well as genetic polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P4502E1 (CYP2E1), on susceptibility to hepatocellular carcinoma (HCC) in Haimen, China. A total of 248 patients with HCC and 248 sex‐, age‐ and residence‐matched population‐based controls were recruited into the study. Virus infection, and ALDH2 and CYP2E1 gene polymorphisms were assessed in 134 paired cases and controls. By univariate analysis, hepatitis B virus (HBV) infection (odds ratio [OR]=9.75; 95% confidence interval [CI] =4.71–20.2), history of intravenous injection (OR=1.50; 95%CI=1.02–2.22), average income (OR=0.63; 95% CI=0.43–0.92), frequent intake of foods rich in protein, e.g., egg (OR=0.6; 95% CI=0.42–0.87), chicken (OR=0.53; 95% CI=0.35–0.79), pork (OR=0.67; 95% CI=0.46–0.98) and fresh fish (OR=0.58; 95% CI=0.39–0.87) significantly differed between cases and controls. However, peanut intake (OR=0.66; 95% CI=0.43–1.01), source of drinking water, including tap (OR=1.33; 95% CI=0.81–2.20), deep well (OR=0.94; 95% CI=0.56–1.55), shallow well (OR=0.85; 95% CI=0.55‐–1.30), river (OR=0.95; 95% CI=0.65–1.38), ditch (OR=1.09; 95% CI=0.76–1.55) and pond water (OR=1.0; 95% CI=0.14–7.10) were not significantly associated with risk. Univariate analysis also indicated that the 1–1 genotype of ALDH2 (OR=1.38; 95% CI=0.86–2.23) as well as the Pst1‐ and Rsa1‐digested c1/c1 genotype of CYP2E1 (OR=1.36; 95% CI=0.81–2.28), was slightly more frequent in the case group. On multivariate analysis, HBV infection (OR=13.9; 95% CI=5.78–33.6) and history of intravenous injection (OR=2.72; 95% CI=1.24–6.00) were still associated with significantly increased risk of HCC, while frequent intake of fresh fish (OR=0.32; 95% CI=0.12–0.86) decreased this risk. These findings suggest that whereas peanut intake, water sources as well as genetic polymorphisms in ALDH2 and CYP2E1 do not significantly correlate with the risk of HCC, HBV infection is a main risk factor, and dietary items rich in protein, especially fresh fish, might protect against the risk of HCC in Haimen, China.

Lack of association between cytochrome P450 2E1 gene polymorphisms and Parkinson's disease in a Chinese population

Lack of association between cytochrome P450 2E1 gene polymorphisms and Parkinson's disease in a Chinese population