BACKGROUND AND OBJECTIVEIt has been proven that cytochrome P450 enzyme 2A13 (CYP2A13) played an important role in the association between single nucleotide polymorphisms (SNP) and human diseases. Cytochrome P450 enzymes are a group of isoenzymes, whose sequence homology may interfere with the study for SNP. The aim of this study is to explore the interference on the SNP study of CYP2A13 caused by homologous sequences.

METHODSTaqman probe was applied to detect distribution of rs8192789 sites in 573 subjects, and BLAST method was used to analyze the amplified sequences. Partial sequences of CYP2A13 were emplified by PCR from 60 cases. The emplified sequences were TA cloned and sequenced.

RESULTSFor rs8192789 loci in 573 cases, only 3 cases were TT, while the rest were CT heterozygotes, which was caused by homologous sequences. There are a large number of overlapping peaks in identical sequences of 60 cases, and the SNP of 101 amino acid site reported in the SNP database is not found. The cloned sequences are 247 bp, 235 bp fragments.

CONCLUSIONThe homologous sequences may interfere the study for SNP of CYP2A13, and some SNP may not exist.

Aryl Hydrocarbon Hydroxylases ; genetics ; Humans ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; genetics

The fields of pharmacogenetics and pharmacogenomics have become increasingly promising regarding the clinical application of genetic data to aid in prevention of adverse reactions. Specific screening tests can predict which animals express modified proteins or genetic sequences responsible for adverse effects associated with a drug. Among the genetic variations that have been investigated in dogs, the multidrug resistance gene (MDR) is the best studied. However, other genes such as CYP1A2 and CYP2B11 control the protein syntheses involved in the metabolism of many drugs. In the present study, the MDR-1, CYP1A2 and CYP2B11 genes were examined to identify SNP polymorphisms associated with these genes in the following four canine breeds: Uruguayan Cimarron, Border Collie, Labrador Retriever and German Shepherd. The results revealed that several SNPs of the CYP1A2 and CYP2B11 genes are potential targets for drug sensitivity investigations.
Animals ; Aryl Hydrocarbon Hydroxylases/*genetics/metabolism ; Cytochrome P-450 CYP1A2/*genetics/metabolism ; Dogs/*genetics/metabolism ; P-Glycoprotein/*genetics/metabolism ; *Polymorphism, Single Nucleotide ; Steroid Hydroxylases/*genetics/metabolism

PURPOSE: The cytochrome P450 2C19 (CYP2C19) metabolizes arachidonic acid to produce epoxyicosanoid acids, which are involved in vascular tone and regulation of blood pressure. Recent findings suggest that CYP2C19 gene might be considered as a novel candidate gene for treatment of cardiovascular disease. The aim of the present study was to evaluate the association between two variants, CYP2C19*2 (681G>A) and CYP2C19*3 (636G>A) and the development of essential hypertension (EH) in Koreans. MATERIALS AND METHODS: We carried out an association study in a total of 1190 individuals (527 hypertensive subjects and 663 unrelated healthy controls). The CYP2C19 polymorphisms were genotyped using the SNaPShot(TM) assay. RESULTS: The distribution of alleles and genotypes of CYP2C19*3 showed significant difference between hypertensive patients and normal controls (p=0.011 and p=0.013, respectively). Logistic regression analysis indicated that the CYP2C19*3 (636A) allele carriers were significantly associated with EH [odds ratio, 0.691; 95% confidence interval (CI), 0.512-0.932, p=0.016], in comparison to wild type homozygotes (CYP2C19*1/*1). Neither genotype nor allele distribution of CYP2C19*2 polymorphism showed significant differences between hypertensive and control groups (p>0.05). CONCLUSION: Our present findings strengthen the evidence of an association between CYP2C19 gene polymorphism and EH prevalence. In particular, the CYP2C19*3 defective allele may contribute to reduced risk for the development of EH.
Adult ; Alleles ; Aryl Hydrocarbon Hydroxylases/*genetics ; Asian Continental Ancestry Group/genetics ; Female ; Genotype ; Homozygote ; Humans ; Hypertension/epidemiology/*genetics ; Logistic Models ; Male ; Middle Aged ; Polymorphism, Genetic/*genetics ; Young Adult

We report a case of intolerance to warfarin dosing due to impaired drug metabolism in a patient with CYP2C9*3/*4. A 73-yr-old woman with atrial fibrilation was taking warfarin. She attained a high prothrombin time international normalized ratio (INR) at the standard doses during the induction of anticoagulation and extremely low dose of warfarin (6.5 mg/week) was finally chosen to reach the target INR. Genotyping for CYP2C9 revealed that this patient had a genotype CYP2C9*3/*4. This is the first Korean compound heterozygote for CYP2C9*3 and *4. This case suggests the clinical usefulness of pharmacogenetic testing for individualized dosage adjustments of warfarin.
Aged ; Anticoagulants/pharmacology ; Aryl Hydrocarbon Hydroxylases/*genetics ; Atrial Fibrillation/*drug therapy/*genetics ; Female ; *Genotype ; Heterozygote ; Humans ; International Normalized Ratio ; Pharmacogenetics ; Polymorphism, Genetic ; Prothrombin Time ; Warfarin/*pharmacology

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

AIMTo investigate the influence of cytochrom P450 CYP2C9 polymorphism on the pharmacokinetics of tolbutamide.

METHODSAn oligonucleotide microarray was designed and fabricated to genotype the CYP2C9 accurately and quickly. 137 healthy volunteers were genotyped with the array to investigate the frequency of CYP2C9 functional SNPs. Moreover, 1 homozygous mutant, 9 heterozygous and 10 wild-genotypes subjects in the assay were selected randomly and sequenced directly. After orally taking tolbutamide, blood samples and urine samples were collected, and their pharmacokinetics was studied with HPLC.

RESULTSCYP2C9 *1/*3 were found in 9 of 137 volunteers, CYP2C9 *3/*3 in only one, others were all CYP2C9 *1/*1 wild types. CYP2C9 *2, CYP2C9 *4 and CYP2C9 *5 alleles were not detected. Direct sequencing of the purified PCR products of the heterozygotes, mutant homozygotes and ten wild type individuals gave a corresponding result to that genotyped by microarray. Pharmacokinetic outcome showed that the individuals with CYP2C9 *1/*3 or CYP2C9 *3/*3 had slower metabolic elimination of tolbutamide than those with CYP2C9 *1/*1.

CONCLUSIONCYP2C9 genetic polymorphism has a significant influence on the pharmacokinetics of tolbutamide. Pharmacogenomic study will be helpful in guiding rational and individualized medication. Key words: tolbutamide; cytochrom P450 CYP2C9; allele; single nucleotide polymorphism; genotyping

Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2C9 ; Genotype ; Heterozygote ; Homozygote ; Humans ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Random Allocation ; Tolbutamide ; pharmacokinetics

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

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.

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.

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).

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.

Adult ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Cytochrome P-450 CYP2C8 ; genetics ; Cytochrome P-450 CYP2E1 ; genetics ; Disease Susceptibility ; Female ; Gout ; enzymology ; ethnology ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Thromboxane-A Synthase ; genetics

OBJECTIVETo describe the clinical and genetic characteristics of a Chinese family with primary angle-closure glaucoma (PACG).

METHODSLinkage analysis and DNA sequencing as well as single strand conformation polymorphism (SSCP) analysis were performed to identify the disease-causing mutations.

RESULTSThe Arg46Stop mutation in MYOC gene and Leu432Val in CYP1B1 gene were identified in all patients. The digenic alterations have not been identified in any same Chinese control individuals.

CONCLUSIONAuthor identified digenic mutations, Arg46Stop in MYOC gene and Leu432Val in CYP1B1 gene, in a Chinese PACG family. Author's studies suggest a possible role of MYOC and CYP1B1 in the development of PACG and support the hypothesis that PAOG and PACG may have common origin across multiple glaucoma phenotypes.

Aged ; Alleles ; Aryl Hydrocarbon Hydroxylases ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Cytochrome P-450 CYP1B1 ; Cytoskeletal Proteins ; genetics ; Eye Proteins ; genetics ; Female ; Genotype ; Glaucoma, Angle-Closure ; genetics ; Glycoproteins ; genetics ; Humans ; Mutation ; Pedigree ; Phenotype ; Polymorphism, Genetic

OBJECTIVETo detect the single nucleotide polymorphisms of clopidogrel metabolism related genes (CYP2C19, ABCB1 and PON1) in Chinese patients with acute coronary syndrome (ACS) by genotype analysis.

METHODSGenetic analysis was performed in patients admitted to Fuwai Hospital from 2005 to 2008 with ACS within 4 weeks. The detection of polymorphisms was performed by TaqMan real-time PCR method. The alleles genotyped were CYP2C19 *2-*8, *17, ABCB1 C3435T, PON1 Q192R and PON1 L55M. Minor allele frequency (MAF) was calculated. Patients were classified as one of the 5 categories by clopidogrel metabolizer phenotypes as extensive [without any "loss-of-function" (LOF) allele *2-*8 or "gain-of-function" (GOF) allele *17], intermediate (with only one LOF allele), Poor (with two or more LOF alleles), ultra (with one or two GOF alleles) or unknown (with one LOF allele and one GOF allele).

RESULTSA total of 2800 ACS patients were enrolled [mean age (59.0 ± 12.3) years and 2236 males (79.9%)]. There were 74% patients with ST-segment elevation myocardial infarction (STEMI, n = 2072), 22.0% patients with non-ST-segment elevation myocardial infarction (NSTEMI, n = 617) and 4.0% patients with unstable angina (UA, n = 111). The minor allele frequency (MAF) for each genotype of CYP2C19 *2, *3, *4, *17 was 28.7%, 4.6%, 0.1% and 1.2%, respectively. There was no LOF allele *5-*8 in the study population. The MAF for ABCB1 C3435T, PON1 Q192R and PON1 L55M was 39.4%, 37.8% and 4.4%, respectively. Clopidogrel metabolizer groups were defined as extensive in 41.7%, intermediate in 45.6%, poor in 10.3%, ultra in 1.9% and unknown in 0.6% patients, respectively. There were no significant differences for all genotypes between males and females. Total LOF carriers of CYP2C19 were 56.4% and GOF carriers were 2.5%.

CONCLUSIONSOur study demonstrated a high distribution of the LOF allele of CYP2C19 in China ACS population.

Acute Coronary Syndrome ; genetics ; metabolism ; Aged ; Alleles ; Aryl Hydrocarbon Hydroxylases ; genetics ; Aryldialkylphosphatase ; genetics ; Asian Continental Ancestry Group ; genetics ; Cytochrome P-450 CYP2C19 ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Ticlopidine ; analogs & derivatives ; metabolism