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Objective:To explore the evaluation of cytochrome P450 2C19 *2 (CYP2C19 *2) gene polymorphism and Helicobacter pylori (Hp) infection for clopidogrel efficacy in patients with coronary heart disease. Methods:The clinical data of 113 patients with coronary heart disease from February 2016 to March 2020 in Suzhou High-tech Zone People′s Hospital were retrospectively analyzed. The CYP2C19 *2 gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, the Hp infection was detected by 13C urea breath test. The patients were treated with clopidogrel, the effect after 4 weeks was evaluated. The receiver operating characteristic (ROC) curve was used to evaluate the CYP2C19 *2 gene polymorphism and Hp infection for evaluating clopidogrel effect in patients with coronary heart disease. Results:The CYP2C19 *2 genotype in patients with coronary heart disease conformed to Hardy-Weinberg balance ( χ2 = 0.33, P>0.05). Among 113 patients with coronary heart disease, Hp infection was in 27 cases, and Hp non-infection in 86 cases. Among Hp infection patients, CYP2C19 *2 gene GG was in 2 cases, GA in 6 cases, AA in 19 cases; among Hp non-infection patients, CYP2C19 *2 gene GG was in 23 cases, GA in 46 cases, AA in 17 cases, there was statistical difference in CYP2C19 *2 gene polymorphism between the two ( χ2 = 24.35, P<0.01). After clopidogrel treatment, effectiveness was in 79 cases, inefficiency in 34 cases. Among effectiveness patients, YP2C19 *2 gene GG was in 20 cases, GA in 43 cases, AA in 16 cases; among inefficiency patients, CYP2C19 *2 gene GG was in 5 cases, GA in 9 cases, AA in 20 cases, there was statistical difference in CYP2C19 *2 gene polymorphism between the two groups ( χ2 = 16.35, P<0.01). The rate of Hp infection in effectiveness patients was significantly lower than that in inefficiency patients: 12.66% (10/79) vs. 50.00% (17/34), and there was statistical difference ( χ2 = 18.23, P<0.05). ROC curve analysis result showed that the area under the curve of CYP2C19 *2 gene polymorphism combined with Hp infection for evaluating clopidogrel effect in patients with coronary heart disease was larger than CYP2C19 *2 gent GG, GA, AA and Hp infection alone evaluating (0.973 vs. 0.869, 0.679, 0.884 and 0.728) . Conclusions:The CYP2C19 *2 gene polymorphism is associated with Hp infection in patients with coronary heart disease, and the CYP2C19 *2 gene polymorphism combined with Hp infection has the evaluation value for the efficacy of clopidogrel.
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Objective To discuss the relationships of the genotype of cytochrome P450 2C19 (CYP2C19) gene and and clopidogrel responsiveness.Methods The study enrolled 110 patients with acute myocardial infarction who were treated with clopidogrel in Tiantan Hospital of Beijing from November 2012 to May 2014.Patients were treated by aspirin and clopidogrel.CYP2C19 polymorphisms were detected by genotype testing kits.Platelet inhibition rates were measured by thrombelastography to represent the antiplatelet effect of clopidogrel.The platelet inhibition rates of clopidogrel were compared among different genotypes.Results Compared with carriers of CYP2C19 * 2 or * 3 reduced-function allele,CYP2C19 * 1 wild type had higher platelet inhibition rate of clopidogrel ((35.73 ± 19.29)％ vs.(48.30± 20.84)％),and the difference was significant(t =3.264,P＜0.05).There was no difference between intermediate metabolizer((35.72± 19.27)％) and poor metabolizer((35.75±19.89)％;P＞0.05).The frequency of wild-type homozygotes CYP2C19 * 1/* 1 was higher in responders than in low responders(frequency of low reaction group CYP2C19 * 1/* 1 14 cases (40.0％),* 1/.2 10 cases(28.6％),* 1/* 3 4 cases(11.4％),* 2/* 2 5 cases(14.3％),* 2/* 3 2 cases (5.7％),frequency of reaction group were 45 cases (60.0％),15 cases (20.0％),4 cases (5.3 ％),7 cases (9.3％),4 cases(5.3％);x2 =3.838,P =0.05).Conclusion Polymorphism of gene CYP2C19 is associated with different responses to clopidogrel.CYP2C19 * 2/ * 3 reduced-function allele is associated with low response to clopidogrel.
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A method for the real-time polymerase chain reaction ( PCR ) coupled with high specific invader assay to detect single nucleotide polymorphism ( SNP) was established. To reduce the background signal, the amount of flap endonuclease 1 ( FEN1 enzyme ) and wild-type detection probe was optimized. Under the optimum conditions including 0. 05 μmo/L invasive oligonucleotide probe, 0. 125 μmol/L wild-type detection probe, 0. 5 μmol/L mutation detection probe, 0. 25 μmol/L each fluorescence resonance energy transfer (FRET) probe and 1. 5 U FEN1, the background signal of wild-type sample and mutation sample was dramatically decreased and the background interference to the detecting results was thus eliminated. A total of 21 cases of aldehyde dehydrogenase-2*2 ( ALDH2*2 ) , 19 cases of cytochrome p450 2 C19*2 ( CYP2 C19*2 ) and 19 cases of CYP2C19*3 were analyzed with the established method, and the genotypes of ALDH2*2 were 10 cases of GG homozygote, 8 cases of GA heterozygote and 3 cases of AA homozygote; the genotypes of CYP2C19*2 were 9 cases of GG homozygote, 8 cases of GA heterozygote and 2 cases of AA homozygote;and the genotypes of CYP2C19*3 were 18 cases of GG homozygote and 1 case of GA heterozygote. These results were consistent with those by pyrosequencing. The established method was specific, simple, short time-consuming and low cost, and could be used for the detection of SNP genotyping with non-polluting in single closed tube.
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Objective To assess the efficacy of triple therapy including proton pump inhibitor (PPI), levofloxacin and amoxicillin for the first-line treatment of H. pylori infection, and the relation between H. pylori eradication and CYP2C19 genetic polymorphism. Methods Two hundred and five H. pylori-positive patients were divided into group E_(20) (esomeprazole 20 mg twice daily), group E_(40)(esomeprazote 40 mg twice daily),group R (rabeprazole 10 mg twice daily) and group L (lansoprazole 30 mg twice daily). Besides PPI, all patients were received levofloxacin 500 mg daily and amoxicillin 1000 mg twice daily for 1 week. The CYP2C19 genotypes were detected in 161 patients. The eradication of H. pylori were analyzed by intention-to-treat (ITT) and per protocol (PP) methods.ResultsThe H. pylori eradication was 86.70% in group E_(20), 88.5% in group E_(40),73.5% in group R and 78.1% in group L. Whereas the H. pylori eradication was 90% in patients with PM genotype,81.5% in patients with HetEM genotype and 82.1% in patients with HomEM genotype. The H.pylori eradication was 83.4% and 79.00% by per protocol (PP) and intention-to-treat (ITT) analyses,respectively. There was no significant difference in H. pylori eradication among four groups (P>0.05), and no relation was found between H. pylori eradication and genotypes (P>0.05). Conclusions PPI based triple therapy was effective in eradication of H. pylori, which is not influenced by CYP2C19 genotypes.
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Genetic polymorphisms in the cytochrome P450 family are widely known to contribute to inter-individual differences in drug pharmacokinetics. In this study we report a case of a patient with cytochrome P450 2C19 polymorphism. A 57-year-old woman presented with right cerebral hemorrhage and left hemiplegia. She was administrated phenytoin (200 mg/day)and phenobarbital (60 mg/day) to prevent convulsions. After a change in phenytoin dosage (97% grains to 10% grains), she developed ataxia and experienced a disturbance in her activities of daily living. She was admitted to our hospital. Her serum concentration of phenytoin was found to be at a toxic level (45.9μg/ml) and serum phenobarbital was relatively high (19.1μg/ml). She showed an extremely low clearance of phenytoin, so we checked the genotype of her P450 2C9 and P450 2C19 cytochromes, which are metabolic enzymes of phenytoin. For cytochrome P450 2C9, the patient was a homozygous extensive metabolizer (wild type, *1/*1), but for cytochrome P450 2C19, she was a poor metabolizer (*3/*3). Her phenytoin dosage was reduced, and her ataxia, activities of daily living, left hemiplegia, and cerebral blood flow in Xe-CT improved.