ABSTRACT
Objective To investigate the relationship between CYP 2C19 gene polymorphisms and clopidogrel efficacy in coronary heart disease patients after percutaneous coronary intervention (PCI).Methods From January 2016 to December 2017,62 patients with acute coronary syndromes and treated with PCI in Guizhou Aerospace Hospital were recruited, CYP2C19 genotype, ADP －induced platelet aggregation rate and myocardial enzymes and other indicators were detected before operation .The myocardial enzymes were measured 24 hours after PCI.According to different metabolic types,the patients were grouped,the above indicators were compared.Results The CYP2C19*1/*1 was 37.10%,CYP2C19*1/*2 was 35.48%,CYP2C19*1/*3 was 11.29%,CYP2C19*2/*2 was 12.90%,CYP2C19*2/*3 was 3.23% and CYP2C19*3/*3 was 0.00%.The LDH,AST,CK,CK－MB and α－HBDH in the PCI patients after operation were significantly higher than those before operation (t＝0.019,0.040, 0.044,0.022,0.014,all P＜0.05).But ADP induced platelet aggregation rate and myocardial enzymes and other indicators among fast metabolism group,intermediate metabolic group and slow metabolic group had no statistically significant differences (all P ＞0.05).Conclusion CYP2C19 mutation frequency in the Chinese population is relatively large,the sample size of this study is less ,the relationship between clopidogrel resistance and the specific genotype can not be obtained ,it need to increase the sample size and comprehensive multi －factor consideration .
ABSTRACT
Background: Thiopurines (azathioprine and 6-mercaptopurine) are highly effective medications but with potential adverse effects. Thiopurine methyltransferase (TMPT) is the key enzyme in their pharmacokinetics and is genetically regulated. A low activity of TPMT is associated with myelotoxicity. The genotype and enzyme activity can vary by ethnicity. Aim: To study the activity and genotype of TPMT in a group of Chilean subjects. Material and Methods: In 200 healthy adult blood donors, TPMT activity was determined by high performance liquid chromatography (HPLC). Deficient, low, normal or high levels were defined when enzymatic activity was < 5, 6-24,25-55 and > 56 nmol/grHb/h, respectively. Genotyping of TPMT (*1, *2, *3A, *3B, *3C) was performed by PCR. Results: Seventy seven women (38.5%) and 123 men (61.5%), with an average age of 34.9 years were studied. Eighteen subjects (9%) had a low enzymatic activity, 178 (89%) had normal activity, 4 (2%) had high activity and no genotype deficient subjects were identified. The wild type genotype (*1) was found in 184 (92%) individuals and 16 (8%) were heterozygous for the variants: *2 (n = 2), *3A (n = 13) and *3C (n = 1). No homozygous subjects for these variants were identified. Wild type genotype had an increased enzymatic activity (40.8 ± 7.2 nmol/gHb/h) compared to heterozygous group (21.2 ± 3 nmol/ gHb/h; p < 0.001). Conclusions: Less than 10% of a Chilean population sample has a low enzymatic activity or allelic variants in the TPMT gene, supporting the use of thiopurines according to international recommendations.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Methyltransferases/genetics , Chile , White People/genetics , White People/statistics & numerical data , Gene Frequency , Genotype , Indians, South American/genetics , Indians, South American/statistics & numerical data , Methyltransferases/metabolism , Phenotype , Polymerase Chain Reaction , Polymorphism, GeneticABSTRACT
Objective To explore the possibility of cytochrome P-450 3A5 (CYP3A5) genotype as a major factor to guide individualized employment of cyclosporin A(CsA) through a comparative study of CsA concentrations in the peripheral blood of hemopoietic stem cell transplant recipients with different CYP3A5 genotypes. Methods Olymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to genotype CYP3A5 gene, and CsA concentrations were detected by a commercial fluorescence polarization immunoassay. Result There were significant differences in CsA concentrations, including standardized trough concentrations C0 and two h peak concentrations C2 , in the two CYP3A5 genotypes found in our samples, and both C0 and C2 in wild homozygotes were lower than heterozygotes. Conclusion CYP3A5 polymorphism is highly associated with CsA concentrations in hemopoietic stem cell transplant recipients, and CYP3A5 genotype may be a predictor to the dose requirement before clinically employment of CsA.