<p>OBJECTIVEA Meta-analysis was performed to assess the association of defective hepatic cytochrome P450 2A6 (CYP2A6) gene with smoking behaviors.p><p>METHODSAll eligible studies published up to 2014 were searched out from PubMed, China National Knowledge Internet (CNKI), ISI Web of knowledge (ISI), vip citation databases (VIP), Chinese BioMedical Literature (CBM) and Elsevier Science Direct, searching words were "smok*","nicotine dependence","CYP2A6","cytochrome P450 2A6","polymorphism","mut*"and"varia*", while 436 articles were concluded. Meta-analysis was performed using Statal 3.1.p><p>RESULTSA total of ten studies were finally included. We didn't find a significant effect of defective CYP2A6 gene on smoking initiation (fixed effect model (FEM): OR = 0.90, 95%CI: 0.78-1.03, I(2) = 25.8%), smoking persistence (random effect model (REM): OR = 0.85, 95%CI: 0.59-1.23, I(2) = 66.3%) and smoking cessation (REM: OR = 0.89, 95%CI: 0.57-1.40, I(2) = 67.1%). But it showed a significant protective effect of CYP2A6*4 on smoking initiation (FEM: OR = 0.78, 95%CI: 0.61-0.99, I(2) = 28.2%), smoking persistence (FEM: OR = 0.53, 95%CI: 0.36-0.77, I(2) = 41.0%) and smoking cessation (REM: OR = 0.49, 95%CI: 0.31-0.80, I(2) = 0.0%).p><p>CONCLUSIONSThis Meta-analysis suggested that there was not a protective effect of defective CYP2A6 gene against smoking behaviors. But smokers with whole CYP2A6 gene deletion would be less likely to start smoking, less smoking persistence and more likely to quit smoking successful than smokers with wild CYP2A6 gene.p>
Aryl Hydrocarbon Hydroxylases ; Asian Continental Ancestry Group ; China ; Cytochrome P-450 CYP2A6 ; Gene Deletion ; Humans ; Polymorphism, Genetic ; Protective Factors ; Smoking ; Smoking Cessation ; Tobacco Use Disorder

Alleles ; Animals ; Aryl Hydrocarbon Hydroxylases ; genetics ; metabolism ; Cytochrome P-450 CYP2A6 ; Humans ; Mixed Function Oxygenases ; genetics ; metabolism ; Nicotine ; metabolism ; Polymorphism, Genetic ; Tobacco Use Disorder ; metabolism

<p>AIMTo establish a HPLC method for determining five major metabolites of caffeine in the urine, 5-acetylamino-6-formylamino-3-methyluracil (AFMU), 1-methylxanthine (1X), 1-methyluric acid (1U), 1,7-dimethyluric acid (17U) and 1,7-dimethylxanthine (17X) and assess the activity of cytochrome P-450 CYP2A6.p><p>METHODSThe contents of five major metabolites of caffeine in the urine were determined by RP-HPLC method. Frequency distribution histogram was drawn by calculating the 17U/(AFMU + 1X + 1U + 17X + 17U) and then evaluated the activity of CYP2A6.p><p>RESULTSThe frequency distribution histograms of CYP2A6 approximately indicated three distinct groups, the cut of point is 0.23 between fast metabolizer and intermediate type. And the cut of point is 0.15 between slow metabolizer and intermediate type.p><p>CONCLUSIONThe method is simple and rapid, suitable for the determination of metabolites of caffeine in urine. The method can be used to assay the activity of CYP2A6.p>
Adult ; Aryl Hydrocarbon Hydroxylases ; metabolism ; Caffeine ; metabolism ; urine ; Chromatography, High Pressure Liquid ; methods ; Cytochrome P-450 CYP2A6 ; Female ; Humans ; Male ; Mixed Function Oxygenases ; metabolism ; Theophylline ; urine ; Uracil ; analogs & derivatives ; urine ; Uric Acid ; analogs & derivatives ; urine ; Xanthines ; urine

Cytochrome P450 2A6(CYP2A6) is known as a major enzyme responsible for C-oxidation of nicotine and 7-hydroxylation of coumarin. The article reviews different alleles of CYP2A6 that have been discovered, their effect on CYP 2A6 activity and the relationship between genetic polymorphism of CYP2A6 and smoking behavior as well as susceptibility of lung and esophageal cancer in different individuals.
Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2A6 ; Esophageal Neoplasms ; enzymology ; genetics ; Genetic Predisposition to Disease ; genetics ; Humans ; Lung Neoplasms ; enzymology ; genetics ; Mixed Function Oxygenases ; genetics ; Polymorphism, Genetic ; Research ; Smoking ; genetics

E2 is a recombinant hepatitis E virus capsid protein including its main antigenic determinants but lacking of the particle assembling domain. P239 was the C-terminal extending protein of E2 and could self-assemble to form virus like particles, which might serve as mimicry of virions both structurally and antigenically. We previously used yeast two-hybrid system to screen proteins interacting with E2 based on a human hepatocyte cDNA library. One candidate was identified as the segment (aa388-437) of cytochrome P450 2A6 protein, which is predominantly expressed in liver and important for metabolization. Some studies have demonstrated that hepatitis virus infection may altered cell metabolic clearance of coumrarin which were rapidly matebolised by CYP2A6. In this research, we demonstrated that the protein interaction between HEV capsid proteins and CYP2A6 by pull-down and co-immunoprecipitation. It was also found that their interaction could decrease the CYP2A6 catalytic activity when p239 was incubated within the CYP2A6-transfected Huh7 cells. These results suggested that CYP2A6 might be related to the pathological process when HEV invaded host cells.
Aryl Hydrocarbon Hydroxylases ; genetics ; metabolism ; Capsid Proteins ; genetics ; metabolism ; Cell Line, Tumor ; Coumarins ; metabolism ; Cytochrome P-450 CYP2A6 ; Hepatitis E virus ; metabolism ; Humans ; Imidazoles ; metabolism ; Immunoprecipitation ; Protein Binding ; Recombinant Proteins ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction