Pingsen Zhao

Effect of cytochrome P450 2C19 polymorphism on adverse cardiovascular events after drug-eluting stent implantation in a large Hakka population with acute coronary syndrome receiving clopidogrel in southern China

Background and objectivesThe objective of this study is to evaluate the effects of cytochrome P450 2C19 (CYP2C19) polymorphism on adverse cardiovascular events (MACE) in Hakka patients with acute coronary syndrome (ACS) receiving clopidogrel who had undergone coronary drug-eluting stent placement after percutaneous coronary intervention (PCI) in southern China.MethodsGenotyping of CYP2C19 and MACE of 934 ACS patients with PCI on clopidogrel maintenance therapy were analyzed. Patients who carried loss-of-function CYP2C19 were treated with a 150-mg maintenance dose of clopidogrel or 90xa0mg of ticagrelor antiplatelet therapy, and patients who were non-carriers received clopidogrel therapy daily at a maintenance dose of 75xa0mg and the patients were followed-up for at least 12xa0months. The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, and target vessel revascularization and stroke.ResultsThe allelic frequency of CYP2C19*2 and CYP2C19*3 of Hakka patients in the current study was 31.64 and 5.19%, respectively. The CYP2C19 wild-type homozygotes (*1/*1) were the most predominant among the patients (40.36%), followed by the CYP2C19*2 heterozygotes (*1/*2) (40.26%). The distribution of CYP2C19 phenotypes was divided into extensive metabolizers (EM; 40.36%), intermediate metabolizers (IM; 45.61%), and poor metabolizers (PM; 14.03%). Based on the genotype-guided antiplatelet therapy, there was no significant association between the carrier status and the clinical outcome at 1, 6, and 12xa0months. In addition, no significant difference in the rates of bleeding was found among the three groups. After logistic regression analysis, hypertension was the only independent predictor of cardiovascular events (relative risk, 1.501; 95% CI, 1.011 to 2.229; Pu2009=u20090.044).ConclusionsOur results shed new light on the important benefit of testing CYP2C19 polymorphisms before prescribing clopidogrel in patients treated with drug-eluting stent implantation after PCI. The testing may help to optimize pharmacotherapy effectiveness by providing individualized treatment to the Chinese population. Our findings mandate further studies aimed at initiating genome-based personalized antiplatelet therapy in a Hakka population in southern China.

Analysis of CYP2C19 Genetic Polymorphism in a Large Ethnic Hakka Population in Southern China

Background Cytochrome P450 (CYP) 2C19 is an enzyme involved in the bioactivation of various important therapeutic drugs, from pro-drugs to an active inhibitor of platelet action. Variants in the CYP2C19 gene influence the pharmacokinetics and clinical response to antiplatelet drugs such as clopidogrel; however, there is no available data about the genetic variation of CYP2C19 in the Hakka population in China. Material/Methods A total of 6686 unrelated participants (ages 17–98 years) of self-reported Hakka ancestry admitted at an inpatient department in a hospital in southern China were successfully genotyped by the gene chip platform. Results The identified allele frequencies were CYP2C19*1 (64.33%), *2 (31.06%) and *3 (4.61%). The major prevalent genotype combinations were CYP2C19 *1/*1 (41.73%) and *1/*2 (39.65%). The distribution of CYP2C19 phenotypes was divided into extensive metabolizers (EM) (41.73%), intermediate metabolizers (IM) (45.21%), and poor metabolizers (PM) (13.06%). In the Hakka population, frequencies of the CYP2C19 *2 and *3 variants were observed to be close to those previously identified in Chinese and several other Asian populations. Conclusions Our study is the first to report on CYP2C19 polymorphisms in the Hakka population, and may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group in the near future.

Molecular prenatal diagnosis of alpha and beta thalassemia in pregnant Hakka women in southern China

To date, there has been no systematic study of DNA‐based prenatal diagnosis of thalassemia in pregnant Hakka women in southern China.

Analysis of SLCO1B1 and APOE genetic polymorphisms in a large ethnic Hakka population in southern China

Statins are the most widely used lipid‐lowering drugs, which have a significant effect on the inhibition of cardiovascular disease. The efficacy and side effects of statins are associated with the polymorphisms of SLCO1B1 and APOE genes. The purpose of this study was to analyze the SLCO1B1 and APOE gene polymorphisms in the Hakka population of southern China.

Molecular Spectrum of α- and β-Thalassemia Mutations in a Large Ethnic Hakka Population in Southern China

Abstract Thalassemia is one of the most prevalent inherited disorders in southern China. However, there have been few reports on molecular characterization of α- and β-thalassemia (α- and β-thal) in the large Hakka population living in Meizhou, a city with high incidence of thalassemia in China. A total of 11,631 in- and outpatients in the Hakka area were analyzed by DNA-based α- and β-thal testing. Of all the samples, 4280 mutant chromosomes were detected, accounting in a total of 35.98%, of which 2864 (24.82%) α-thal mutants were detected, 1268 (10.09%) β-thal mutants were detected, 148 (1.27%) α- and β-thal mutants were detected. The following mutations – –SEA/αα (Southeast Asian deletion), βA/βA; αα/αα, IVS-II-654 (C>T) (HBB: c.316-197C>T)/βA; αα/αα, codons 41/42 (–TCTT) (HBB: c.126_129delCTTT)/βA; and –α3.7/αα, βA/βA were the most common thalassemia genotypes. The most common thalassemia genotype in the Hakka population in Meizhou was α-thal. In order to reduce the incidence of severe thalassemia in children, a prevention and control strategy should be established based on the distribution data of thalassemia genotyping. Our findings provide a valuable reference for clinical institutions or local governments to reduce the prevalence of thalassemia in the subtropical regions in the world.

Effects of different CYP2C19 genotypes on prognosis of patients complicated with atrial fibrillation taking clopidogrel after PCI

The effects of different cytochrome P450 2C19 (CYP2C19) genotypes on the prognosis of clopidogrel resistance in patients complicated with atrial fibrillation taking clopidogrel after percutaneous coronary intervention (PCI) were investigated. Eighty patients who were complicated with atrial fibrillation and treated with clopidogrel antiplatelet therapy after PCI in Meizhou Hospital Affiliated to Zhongshan University from September 2015 to January 2017 were selected, and divided into two groups according to the CYP2C19 genotype: extensive metabolism (EM) group and poor metabolism (PM) group. The related risk factors of clopidogrel resistance were determined, and the platelet aggregation rate and clopidogrel resistance rate were compared between the two groups during treatment. Non-fatal myocardial infarction and serious life-threatening complications in the two groups were observed. The increased total cholesterol level and the history of smoking and drinking were the independent risk factors of atrial fibrillation after PCI. The platelet aggregation rates in the EM group at 1, 3 and 12 months after medication were significantly lower than those in the PM group in the same period (P<0.05). The clopidogrel resistance rates in EM group before medication and at 1, 3 and 12 months after medication were higher than those in PM group in the same period (P<0.05). The onset time of non-fatal myocardial infarction in EM group was earlier than that in PM group (P<0.05), the infarct area was larger than that in PM group (P<0.05), and the left ventricular ejection fraction (EF) after onset was lower than that in PM group (P<0.05). In conclusion, the increased total cholesterol level and the history of smoking and drinking are the independent risk factors of clopidogrel resistance in patients complicated with atrial fibrillation after PCI. The incidence rates of cardiac complications are increased significantly in patients with PM CYP2C19 genotype.

Prevalence and genotype distribution of human papillomavirus infection among women in northeastern Guangdong Province of China

BackgroundHuman papillomavirus (HPV) DNA testing is an important method in cervical cancer screening. However, the studies on prevalence and genotype distribution of HPV among women in northeastern Guangdong Province of China are very limited.MethodsA total of 28,730 women attending the Department of Gynecology of Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University between January 1st, 2013 and June 1st, 2015 were enrolled in this study. HPV type-specific distribution was tested using flow-through hybridization and gene chip.ResultsThe overall prevalence of HPV infection was 19.81%, among which 79.09% were infected with high-risk HPV subtypes in the subjects. The 5 most predominant genotypes were HPV16, 52, 58, 18 and 81. Most HPV infections were observed in women aged 41–50 and women aged 30–59 accounted for a proportion of over 80%.ConclusionsOur findings suggested a high burden of HPV infection among women in northeastern Guangdong Province of China. We identified the top 5 HPV genotypes as well as the age-specific distribution of HPV infections in this area.

Serum lipid profiles in patients with acute myocardial infarction in Hakka population in southern China

BackgroundLittle is known about serum lipid levels comparison of patients with acute myocardial infarction (AMI) in Hakka patients in southern China. To estimate the prevalence lipid profiles in Hakka patients with AMI in southern China.MethodWe analyzed 1382 patients with a first AMI in Hakka patients in southern China between Jan. 2015 and Dec. 2015.ResultsOur findings demonstrated that low-density lipoprotein cholesterol (LDL), total cholesterol (TC), and triglyceride (TG) were higher in nonelderly than in elderly for males. There were significant differences in TC, LDL, HDL, and TG among various age groups for both males and female patients (Pu2009<u2009.05). TC, LDL, HDL, and TG were higher in females than males for the elderly, and the LDL levels of females were higher in 70–79,80–89xa0year age groups than males. The HDL level of female patients was higher than males in those 50–59, 60–69, and 70–79xa0year age groups. Compared with males, females had higher level of TG in the 60–69, 70–79, and 80–89xa0year age groups and had higher level of TC in the 50–59, 70–79, and 80–89xa0year age groups, respectively. Isolated high TG (normal LDLu2009+u2009normal HDL+ high TG) was most common type of combined dyslipidemia for female elderly (22.2%), female nonelderly (23.2%) and male elderly (24.1%) patients.ConclusionOur results confirmed that serum lipid levels varied in age and gender in Hakka patients with acute myocardial infarction. Dyslipidemia is more prevalent in the non-elderly than in the elderly for males. Levels of TC, LDL, HDL, and TG were higher in females than males for the elderly Hakka population in southern China.