1.Effects of the flavonoids on cytochrome P-450 CYP1, 2E1, 3A4 and 19.
Acta Pharmaceutica Sinica 2007;42(1):8-12
Flavonoids are present in fruits, vegetables and beverages derived from plants, and in many dietary supplements or herbal remedies. A number of naturally occurring flavonoids have been shown to modulate the CYP450 system, including the induction or inhibition of these enzymes. This review focuses on the flavonoid effects on cytochrome P450 (CYP) enzyme CYP1, 2E1, 3A4 and 19. Flavonoids alter CYPs by various mechanisms, including the stimulation of gene expression via specific receptors and/or CYP protein, or mRNA stabilization and so on. But in vivo and in vitro, the effects of flavonoids are not always coincident as a result of concentrations of flavonoids, genetic and environmental factors. As well, flavonoids may interact with drugs through the induction or inhibition of their metabolism. Much attention should be paid to the metabolism interaction of the flavonoids when coadministered with other drugs.
Animals
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Aromatase
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genetics
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metabolism
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Cytochrome P-450 CYP1A1
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antagonists & inhibitors
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genetics
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metabolism
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Cytochrome P-450 CYP2E1
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genetics
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metabolism
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Cytochrome P-450 CYP2E1 Inhibitors
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Cytochrome P-450 CYP3A
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genetics
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metabolism
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Cytochrome P-450 CYP3A Inhibitors
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Cytochrome P-450 Enzyme Inhibitors
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Cytochrome P-450 Enzyme System
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genetics
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metabolism
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Enzyme Activation
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drug effects
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Flavonoids
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pharmacology
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Humans
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RNA, Messenger
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genetics
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metabolism
2.Effect of hepatocyte cytochrome P450 2E1 gene and its expression in nonalcoholic steatosis in rats.
Hong-Tao SHI ; Dong-Feng CHEN ; Tao LI ; Ren-Ping XIONG
Chinese Journal of Hepatology 2005;13(2):154-155
Animals
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Cytochrome P-450 CYP2E1
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biosynthesis
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genetics
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Fatty Liver
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genetics
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Liver
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metabolism
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Male
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Rats
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Rats, Wistar
4.Relationship between gene polymorphism of CYP2E1, CYP1A1, IL-4 and medicamentosa-like dermatitis induced by trichloroethylene.
Xin-yun XU ; Guan-hao CHEN ; Nan WU ; Lei YU ; Fang HUANG ; Lin-qing YANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2009;27(2):71-73
<p>OBJECTIVETo investigate the relationship between gene polymorphism of CYP2E1, CYP1A1, IL-4 and susceptibility of medicamentosa-like dermatitis induced by trichloroethylene (TCE).p><p>METHODS35 patients with medicamentosa-like dermatitis induced by TCE were chosen as the patient group, and 35 healthy workers as control group. The real-time quantitative polymerase chain reaction (PCR) with TaqMan minor groove binding (MGB) probes was used to test single nucleotide polymorphisms (SNP) of CYP2E1, CYP1A1 and IL-4 in the patients with medicamentosa-like dermatitis as well as in the control. The genotypes and the frequency of genotype or allele were compared between the patients and control with statistical analysis.p><p>RESULTSThe frequency of allele G within CYP1A1 gene (rs1048943) was significantly higher in TCE patients (37.1%) than that in control (P<0.05); the frequency of allele T within CYP2E1-1053 C/T was significantly higher in TCE patients (41.4%) than that in control (P<0.01); the frequency of T/T within IL-4-588 C/T (rs2243250) was significantly higher in TCE patients (75.0%) than that in control (P<0.01), and the frequency of allele T within IL-4-588 C/T (rs2243250) was also significantly higher in TCE patients (87.5%) than that in control (P<0.01).p><p>CONCLUSIONThe gene polymorphism of CYP2E1, CYP1A1, IL-4 is probably associated with hypersensitivity for the TCE patients with medicamentosa-like dermatitis, and could be one of the genetic factors related to the individual susceptibility to TCE exposure.p>
Cytochrome P-450 CYP1A1
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genetics
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Cytochrome P-450 CYP2E1
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genetics
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Dermatitis, Occupational
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genetics
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Genetic Predisposition to Disease
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Humans
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Interleukin-4
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genetics
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Polymorphism, Single Nucleotide
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Trichloroethylene
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adverse effects
5.Genetic polymorphisms of the CYP450 1A1, CYP450 2E1, GSTM1, GSTT1, and GSTP1 in Korean.
Qing-song XU ; Yun-Chul HONG ; Kuan-Hee LEE
Chinese Journal of Medical Genetics 2005;22(3):347-349
<p>OBJECTIVEThis is an investigation on the polymorphism distribution of genes related with metabolism, such as cytochrome P450 1A1 (CYP1A1), CYP2E1, glutathione S-transferase M1 (GSTM1), GSTT1 and GSTP1 among the Korean public.p><p>METHODSThe techniques of polymerase chain reaction-restriction fragment length polymorphism were adopted. The authors analyzed the polymorphisms for 3-flanking region of CYP1A1 gene by the restriction endonuclease MspI, for 5-flanking region of the gene of CYP2E1 by PstI, for GSTP1 by BsmAI, and for the presence of GSTM1 and GSTT1 genotype to evaluate the gene types and calculate their frequencies in 300 healthy university students.p><p>RESULTSThe CYP1A1 genotype frequencies for types of m1/m1, m1/m2, and m2/m2 are 39.7%, 49.7%, and 10.7% respectively, with the allele frequencies 0.645 for m1 and 0.355 for m2. The CYP2E1 genotype frequencies are 66.7% for type of c1/c1, 30% for type of c1/c2, 3.3% for type of c2/c2 with the allele frequencies 0.818 for C1 and 0.182 for C2. The null type frequency is 53.3% for gene GSTM1 and 54.7% for gene GSTT1. The genotype frequencies of GSTP1 is 62% for the type of Ile/Ile, 34.3% for the type of Ile/Val, 3.7% for the type of Val/Val, and the allele frequencies are 0.792 for IIe and 0.208 for Val. All of the gene distribution matched the equilibrium law of Hardy-Weinberg.p><p>CONCLUSIONThe genetic distribution of the genes in Korean is similar to the distribution of those in Chinese; more than half of the Korean in the study sample lack GSTM1 and GSTT1; the frequency for GSTM1 and GSTT1 null type of Korean is 3 times that of Indian.p>
Adolescent
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Adult
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Aged
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Asian Continental Ancestry Group
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genetics
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Cytochrome P-450 CYP1A1
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genetics
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Cytochrome P-450 CYP2E1
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genetics
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Female
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Gene Frequency
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Genotype
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Glutathione S-Transferase pi
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genetics
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Glutathione Transferase
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genetics
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Humans
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Korea
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Male
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Middle Aged
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Polymorphism, Genetic
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genetics
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Young Adult
6.Association of single nucleotide polymorphisms of cytochrome P450 gene with susceptibility to gout in ethnic Han males from coastal regions of Shandong province.
Lin HAN ; Guizhi MAO ; Ying CHEN ; Changgui LI ; Zhen LIU ; Yao WANG ; Xinde LI ; Mingxia SUN ; Wei REN ; Xuefeng WANG ; Zhaotong JIA
Chinese Journal of Medical Genetics 2015;32(4):538-542
<p>OBJECTIVETo assess the association of cytochrome P450 gene single nucleotide polymorphisms (SNPs) with susceptibility to gout in ethnic Han males from coastal regions of Shandong province.p><p>METHODSFour hundred and eighty male patients with gout and 480 healthy male controls were included. Genotyping was carried out with a custom Illumina GoldenGate Genotyping assay to detect SNP rs2275620 of CYP2C8 gene, SNP rs2070676 of CYP2E1 gene, SNP rs837395 of CYP4B1 gene, and SNP rs194150 of TBXAS1 gene. The association was assessed with chi-square test.p><p>RESULTSNo significant difference has been found between the two groups in regard to the genotypic and allelic frequencies of the TT, AT, AA genotypes and A, T alleles of the SNP rs2275620 of the CYP2C8 gene (P=0.88; P=0.97), the CC, CG, GG genotypes and C,G alleles of SNP rs2070676 of the CYP2E1 gene (P=0.24; P=0.09), the TT, AT, AA genotypes and A, T alleles of SNP rs837395 of the CYP4B1 (P=0.88; P=0.97), and TT, AT, AA genotypes and the A,T alleles of SNP rs194150 of TBXAS1 gene (P=0.15; P=0.06).p><p>CONCLUSIONThis study has identified no association of SNP loci rs2275620(A/T) of CYP2C8, rs2070676(C/G) of CYP2E1, rs837395(A/T) of CYP4B1 and rs194150(A/T) of TBXAS1 with gout in ethnic Han males from coastal regions in Shandong province. However, our result needs to be replicated in larger sets of patients collected from other regions and populations.p>
Adult
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Aryl Hydrocarbon Hydroxylases
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genetics
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Asian Continental Ancestry Group
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ethnology
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genetics
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China
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ethnology
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Cytochrome P-450 CYP2C8
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genetics
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Cytochrome P-450 CYP2E1
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genetics
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Disease Susceptibility
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Female
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Gout
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enzymology
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ethnology
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genetics
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Humans
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Male
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Middle Aged
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Polymorphism, Single Nucleotide
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Thromboxane-A Synthase
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genetics
7.Expression of human CYP2E1 in insect cells using bac-to-bac expression system.
Ke LU ; Su ZENG ; Tong-wei YAO
Journal of Zhejiang University. Medical sciences 2008;37(2):118-125
<p>OBJECTIVETo obtain recombinant human CYP2E1 and to determine its activity by using the specific probe substrate.p><p>METHODSCYP2E1 cDNA was obtained by RT-PCR using human liver RNA as template. The cloned CYP2E1 cDNA was ligated with pFastBac vector to generate recombinant pFastBac-CYP2E1, which was then transformed into E. coli DH 10 Bac. Recombinant Bacmid-CYP2E1 was generated by transposition. Then Spodoptera frugiperda (Sf9) insect cells was infected with Bacmid-CYP2E1 to generate recombinant baculoviruses carrying human CYP2E1 cDNA. Finally, Sf9 insect cells were triinfected with recombinant baculoviruses carrying human CYP2E1, CYPOR and CYPb5. The activity of the recombinant enzymes was determined using chlorzoxazone as the substrate.p><p>RESULTThe Kmand Vmaxof recombinant CYP2E1 to chlorzoxazone was (72.4 +/-8.7) micromol. L(-1) and (2.41 +/-0.10) micromol.min(-1)?g(-1)protein, respectively.p><p>CONCLUSIONActive recombinant CYP2E1 has been obtained by bac-to-bac expression system and its activity is similar to previous reports.p>
Animals
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Baculoviridae
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genetics
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metabolism
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Cytochrome P-450 CYP2E1
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biosynthesis
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genetics
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Escherichia coli
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genetics
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Genetic Vectors
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genetics
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Humans
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Recombinant Fusion Proteins
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biosynthesis
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genetics
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Spodoptera
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genetics
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metabolism
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Transfection
8.Liver Tissue-specific Genes IGFALS,CYP3A4,SLC22A1 and CYP2E1 May be Associated with Poor Prognosis of Liver Cancer.
Yan-Yan ZHANG ; Jing CAO ; Xiao-Tong CHEN ; Jun-Hui CHEN ; Yu-Bao ZHENG
Acta Academiae Medicinae Sinicae 2021;43(3):371-381
Objective To explore the function and mechanism of related genes in the occurrence and development of liver cancer, and the possibility of key genes as potential biomarkers and prognostic indicators for the treatment of liver cancer.Methods We selected 4 datasets(GSE57957, GSE121248, GSE36376 and GSE14520)from the GEO database.With
Biomarkers, Tumor/genetics*
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Carrier Proteins
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Computational Biology
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Cytochrome P-450 CYP2E1
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Cytochrome P-450 CYP3A
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic
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Gene Regulatory Networks
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Glycoproteins
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Humans
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Liver Neoplasms/genetics*
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Prognosis
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Protein Interaction Maps
10.Correlation of polymorphisms of adiponectin receptor 2 gene +33371Gln/Arg, cytochrome P4502E1 gene Rsa I and smoking with nonalcoholic fatty liver disease.
Journal of Southern Medical University 2014;34(10):1481-1487
<p>OBJECTIVETo investigate the correlation of the polymorphisms of adiponectin receptor 2 (AdipoR2) gene +33371Gln/;Arg and cytochromes P4502E1 gene Rsa I (CYP2E1-Rsa I) as well as smoking with nonalcoholic fatty liver disease (NAFLD).p><p>METHODSThe polymorphisms of AdipoR2 gene +33371Gln/Arg and CYP2E1-Rsa I were analyzed with PCR technique in peripheral blood leukocytes from 750 NAFLD cases and 750 healthy subjects.p><p>RESULTSThe frequencies of AdipoR2 gene +33371Gln/Arg (A/A) and CYP2E1-Rsa I (c2/c2 ) were 39.20% and 71.73% in NAFLD cases, respectively, significantly higher than those in healthy subjects (21.07% and 43.07%, respectively, P<0.01). The risk of NAFLD increased significantly in subjects carrying +33371Gln/Arg (A/A) (OR=2.4156, 95% CI=1.8164-4.0725) and CYP2E1-Rsa I (c2/c2) (OR=3.3547, 95% CI=1.9182-4.5057). Combined analysis of the polymorphisms showed that the percentage of +33371Gln/Arg (A/A)/CYP2E1-Rsa I (c2/c2) was 32. 67% in NAFLD cases, significantly higher than that in the healthy subjects (6.40%, P<0.01), and subjects carrying both +33371Gln/Arg (A/A) and CYP2E1-Rsa I (c2/c2) had a high risk of NAFLD (OR=9.9264, 95% CI=4.2928-12.4241). The smoking rate was significantly higher in the case group than in the control group (OR=2.5919, 95% CI=1.4194-4. 9527, P<0.01), and statistical analysis suggested an interaction between smoking and +33371Gln/Arg (A/A)/CYP2E1-Rsa I (c2/c2) to increase the risk of NAFLD (OR=34.6764, 95% CI=18.9076-61.5825).p><p>CONCLUSION+33371Gln/Arg (A/A), CYP2E1-Rsa I (c2/c2 ) and smoking are risk factors for NAFLD and coordinately contribute to the occurrence of NAFLD.p>
Alleles
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Case-Control Studies
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Cytochrome P-450 CYP2E1
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genetics
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Humans
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Non-alcoholic Fatty Liver Disease
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genetics
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Polymorphism, Genetic
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Receptors, Adiponectin
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genetics
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Risk Factors
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Smoking