<p>OBJECTIVETo study the cytochrome P450 2C19(CYP2C19) gene polymorphism in 4 Chinese nationality populations.p><p>METHODSThe genotypes of the unrelated Miao, Buyi, Tu and Dulong subjects were analyzed by polymerase chain reaction and restriction fragment length polymorphism (RFLP).p><p>RESULTSCYP2C19*2 allele frequencies were 0.291, 0.329, 0.315 and 0.349 in Miao, Buyi, Tu and Dulong population, respectively. The four populations were consistent with Hardy-Weinberg expectations (P>0.05).p><p>CONCLUSIONThe frequencies of CYP2C19*2 were in agreement with those of other published data on Asian, but were different from those data on European and African.p>
African Continental Ancestry Group ; genetics ; Aryl Hydrocarbon Hydroxylases ; Asian Continental Ancestry Group ; genetics ; China ; ethnology ; Cytochrome P-450 CYP2C19 ; Cytochrome P-450 Enzyme System ; genetics ; European Continental Ancestry Group ; genetics ; Gene Frequency ; Genetics, Population ; Humans ; Mixed Function Oxygenases ; genetics ; Polymerase Chain Reaction ; methods ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length

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

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

<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

<p>OBJECTIVETo assess the contribution of vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genotype, age, body size, height, and weight to warfarin dose requirement.p><p>METHODSBlood samples were collected from 191 patients receiving warfarin therapy. Patients's age, gender, height, and weight were registered. PCR-RFLP method was used for the detection of VKORC1-1639G > A and CYP2C9 genotype.p><p>RESULTSVKORC1-1639G > A genotyping showed that 159 patients were homozygous AA, 31 were heterozygous GA, and 1 was homozygous GG genotype. CYP2C9 genotyping showed that 176 patients were *1/*1, 15 patients were heterozygous *1/*3. Patients with VKORC1-1639 (G > A) GG + GA genotype required a significantly higher warfarin dose than those with AA genotype [(3.36 +/- 0.97) mg/d vs. (1.75 +/- 0.56) mg/d, P < 0.01], and patients with CYP2C9*1/*1 genotype also required a higher warfarin dose than those with CYP2C9*1/*3 genotype [(2.06 +/- 0.83) mg/d vs. (1.55 +/- 1.32) mg/d, P < 0.05]. The multiple linear regression model for warfarin dose indicated age, weight and VKORC1 genotype could explain the inter-individual variation in dose requirement of 9.3%, 7.4%, 51.9% patients, respectively; age, weight, CYP2C9 and VKORC1 genotype together could explain the inter-individual variation in dose requirement of 64.1% patients.p><p>CONCLUSIONThis study showed that age, weight and VKORC1 and CYP2C9 polymorphism had significant influences on warfarin dose requirements and should be considered on dosing regimens modification to improve the safety of warfarin therapy.p>
Adult ; Aged ; Aged, 80 and over ; Anticoagulants ; therapeutic use ; Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2C9 ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Mixed Function Oxygenases ; genetics ; Polymorphism, Genetic ; Treatment Outcome ; Vitamin K Epoxide Reductases ; Warfarin ; therapeutic use

<p>AIMTo assess the effect of gender on genetic polymorphism of cytochrome CYP2C19 in Chinese population.p><p>METHODSThe genetic polymorphism of 140 healthy Chinese were analysed by PCR-RFLP (restriction fragment length polymorphism).p><p>RESULTSOf 52 genotyped male subjects, 23 (44.23%) were homozygous for wildtype (wt/wt), 6 (11.54%) were homozygous for CYP2C19 m1 (m1/m1), and 23 (44.23%) were heterozygous for CYP2C19 m1 or CYP2C19 m2 (wt/m1 or wt/m2); and among the 88 genotyped female subjects, 31 (35.23%) were homozygous for wildtype (wt/wt), 13 (14.82%) were homozygous for CYP2C19 m1 (m1/m1), and 44 (50.0%) were heterozygous for CYP2C19 m1 or CYP2C19 m2 (wt/m1 or wt/m2); no homozygous genotype for CYP2C19 m2 (m2/m2) was found in the study.p><p>CONCLUSIONThere is no statistical difference in ocurance of wt/wt and m1/m1 between in male and in female, so gender have no significant effect on genetic polymorphism of cytochrome CYP2C19.p>
Adolescent ; Adult ; Aged ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; China ; Cytochrome P-450 CYP2C19 ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Mixed Function Oxygenases ; genetics ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Sex Factors

<p>BACKGROUNDPatients with the genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A are expected to require the lowest dose of warfarin, and to have a greatly increased risk of bleeding. The experience for the dosing of warfarin in such extremely rare cases has been seldom reported.p><p>METHODSDemographic and clinical data from two cases with stable low dose of warfarin in China were studied by resequencing the corresponding gene segments in their whole blood DNA. The potential clinical value of the pharmacogenetic algorithm for them was evaluated by calculating the stable dose of warfarin in pharmacogenetic algorithm developed by International Warfarin Pharmacogenetics Consortium.p><p>RESULTSBoth cases (68-year-old female and 50-year-old male) were diagnosed as chronic nonvalvular atrial fibrillation needing warfarin treatment, with target international normalized ratio (INR) 2 to 3. Case 1 had stable warfarin dose of 0.625 mg/d and case 2 1.25 mg/d. They needed more than 1 month to stabilize their anticoagulation. Exceeding INR values were recorded for them when the dose of warfarin was no more than 2 mg/d. Hemorrhagic complication appeared in case 1 when the dose was titrated from 2.5 to 1.25 mg/d. No concomitant medicine to increase or decrease the INR value was recorded for them. Genotyping CYP2C9 and VKORC1 showed both patients were the carriers of the homozygous alleles -CYP2C9*3/*3 and VKORC1-1639 A/A. Their stable doses of warfarin calculated by the pharmacogenetic dose algorithm (0.672 mg/d for case 1 and 1.16 mg/d for case 2) were comparable with their actual stable therapeutic doses.p><p>CONCLUSIONSTwo Chinese with the rare genotypes of both CYP2C9*3/*3 and VKORC1-1639 A/A were found to require the extremely low dose of warfarin. The pharmacogenetic algorithm incorporating the variances of VKORC1 and CYP2C9 genotypes, as well as the non-genetic factors could predict their stable dose of warfarin with high accuracy.p>
Aged ; Anticoagulants ; adverse effects ; Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2C9 ; Female ; Genotype ; Hemorrhage ; chemically induced ; Humans ; Male ; Middle Aged ; Mixed Function Oxygenases ; genetics ; Pharmacogenetics ; Vitamin K Epoxide Reductases ; Warfarin ; adverse effects

Interests on the effects of cytochrome P450 (CYP450) monooxygenases and epoxyeicosatrienoic acids (EETs) on myocardial ischemic-reperfusion injury has been increased in recent years. The CYP450/EET system may influence the degree of myocardial ischemic-reperfusion injury through "poly-targets", such us oxygen free radical, calcium overload, leukocytes adherence, nitric oxide, ATP-sensitive K+ channels, and mitogen activated protein kinase. The exaggeration or recovery of injury depends on the physical status. Study of factors that affects CYP450/EET, particularly identification of their involvement in cardioprotective signaling and specific roles, will elucidate the mechanisms of myocardial ischemic-reperfusion injury, and find a new way of prevention and treatment. This article will review the relationship between the changes of CYP450/EETs system and myocardial ischemic-reper-
Animals ; Cytochrome P-450 Enzyme System ; metabolism ; Eicosapentaenoic Acid ; metabolism ; Humans ; Mixed Function Oxygenases ; metabolism ; Myocardial Reperfusion Injury ; etiology ; metabolism

Aims: Lytic polysaccharide monooxygenase (LPMO) is an enzyme capable of cleaving glycoside bonds of recalcitrant polysaccharides through an oxidative mechanism. LPMO activity, in synergy with hydrolytic enzymes, increases the production of monomer sugars from the biodegradation of lignocellulose. This study was aimed at evaluating actinomycete S2 strain LPMO activity based on the release of xylose as one of reducing sugar and hydrogen peroxide (H2O2) in the course of lignocellulosic biodegradation. Methodology and results: The oxidation activity of LPMO from actinomycete S2 strain was measured by using the substrate of Avicel supplemented with ascorbic acid and copper ions (Cu2+) to identify its effect on the release of xylose as one of reducing sugar. The optimum incubation time for the LPMO production was also conducted. Further, H2O2 quantitative analysis was performed as by-product of LPMO activity and 16S rRNA gene sequence of actinomycete S2 strain were subsequently determined. We found that supplementation of 1 mM ascorbic acid and 0.2 mM Cu2+ increased xylose as one of reducing sugar production by up to 5-fold from 255.03 to 1290 μg/mL after an optimal incubation period of 6 days. Based on H2O2 production, the LPMO activity of actinomycete S2 strain was 0.019 ± 0.001 U/mL. There is likelihood that LPMO activity derived from actinomycete S2 strain has a synergistic effect with the activity of other lignocellulose-degrading enzymes. This actinomycete showed 99% similarity to the 16S rRNA gene sequence of Streptomyces avermitilis strain EAAG80. Conclusion, significance, and impact of study LPMO enzyme activity from actinomycete S2 strain as determined by the production of reducing sugar and H2O2 was greatly increased by supplementation with ascorbic acid as an electron donor and Cu2+ ions. To the best of our knowledge, this is the first elucidation of LPMO activity from an indigenous Indonesian actinomycete.
Mixed Function Oxygenases--metabolism ; Lignin--metabolism

Warfarin is a frequently prescribed anticoagulant in rehabilitation patients. Adverse drug reactions of warfarin were reported as bleeding and cutaneous microvascular thrombosis. Major bleeding, such as intracranial hemorrhage and psoas hematoma, in patients receiving anticoagulation therapy is a rare condition, but sometimes very serious complication that can even be fatal. Patient-specific factors (eg, age, body size, race, concurrent diseases, and medications) explain some of the individual variability in warfarin dose, but genetic factors, which influence warfarin response, explain a significantly higher proportion of the variability in the dose. There are two identified genes that are responsible for the main proportion of the genetic effect: CYP2C9, which codes for the enzyme cytochrome P450 2C9 that metabolizes S-warfarin, and VKORC1, which codes for warfarin's target, vitamin K epoxide reductase. We report a case of intolerance to warfarin dosing, due to impaired drug metabolism in a patient with CYP2C9*1/*3 and VKORC 1173TT. Fortunately, there are no severe complications.
Body Size ; Continental Population Groups ; Cytochrome P-450 Enzyme System ; Drug Toxicity ; Hematoma ; Hemorrhage ; Humans ; Intracranial Hemorrhages ; Mixed Function Oxygenases ; Oxidoreductases ; Thrombosis ; Vitamin K ; Warfarin