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A Study On The Relationship Between Lipid Metabolism,Drug Metabolism Gene Mutation And Platelets To Lymphocytes Ratio With Acute Coronary Syndrome

Posted on:2019-07-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:H LiFull Text:PDF
GTID:1364330548956479Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective:(1)The aim of this study is to investigate whether the platelet-tolymphocyte ratio(PLR)is an independent predictor of all-cause mortality and cardiovascular events in patients with acute coronary syndrome(ACS).(2)We analyzed the polymorphism of cytochrome P450(CYP2C19)gene in Han and Uygur ACS patients in Xinjiang area,and compared the gene phenotypic difference and gene frequency distribution between Han and Uygur population.We further explored the association between CYP2C19 gene polymorphism and PLR in Xinjiang area,and studied whether all two factors were risk factors for ACS and whether there was interaction between the gene and other cardiovascular risk factors.(3)The aim of this study was to explore the relationship among the rs738409 polymorphism of PNPLA3 gene,PLR and acute coronary syndrome and analyzed the interaction between PNPLA3 gene polymorphism and other cardiovascular risk factors on the acute coronary syndrome.Methods:(1)PubMed,Embase,and the Cochrane Library were searched for relevant cohort studies regarding the association between PLR and outcomes of patients with ACS.Either a random-or a fixed-effect model was used for pooling data.(2)The study includes 1763 patients with acute coronary syndrome who received blood genomic DNA extraction kit instructions to extract genomic DNA,cDNA microarray technology to detect two ethnic study population CYP2C19 genotype and allele frequencies in the First Affiliated Hospital of Xinjiang Medical University in two years(November in 2015 until November in 2017),Han group 916 cases,847 cases of Uygur,according to the CYP2C19 gene polymorphism of metabolic function type,the CYP2C19 gene was divided into fast metabolism genotype(CYP2C19* 1/* 1),intermediate metabolism genotype(CYP2C19* 1/* 2 and *1/* 3)and slow metabolism genes type(CYP2C19 * 2/* 2?* 2/* 3* and 3/* 3).According to disease types,they were divided into non-ST segment elevation acute coronary syndrome and ST segment elevation acute coronary syndrome.This was a hospital-based case-control study,a total of 615 hospitalized Participants of our hospital,314 cases of acute coronary syndrome group(from 1763 patients with ACS),the control group of 301 cases,non ST elevation ACS patients with 207 cases,ST segment elevation ACS 107 cases,the patients have conducted routine blood test,biochemical examination and determination of CYP2C19 gene and coronary angiography.(3)This was a hospital-based case-control study,there are 301 acute coronary syndromes patients who hospitalized in our hospital from 1763 ACS patients,and 305 patients with normal coronary artery disease in the same period.The blood routine,biochemical indexes,PNPLA3 rs738409 gene polymorphisms were detected.Results:(1)Eight studies involving 6627 patients with ACS were included.The cutoff PLR value for defining risk groups was 150,and patients were assigned to the low(?150)or high(>150)PLR groups.The pooled relative risk(RR)values of in-hospital and long-term mortality were 2.15 [95%CI(confidence interval),1.73-2.67;P<0.00001] and 2.27(95%CI,1.35-3.80;P=0.002),respectively,comparing the high and the low PLR groups.Compared with the low PLR group,the high PLR group had a significantly increased risk of in-hospital(RR,1.95;95%CI,1.30-2.91;P=0.001)and long-term(RR,1.50;95%CI,1.08-2.09;P=0.01)major adverse cardiovascular events.(2)The distribution of CYP2C19 genotype is not related to age and sex.The frequency of ACS distribution in Han nationality in Xinjiang area is 18.15%,31.19%and 2.61%respectively,and the Uygur population was 29.15%,18.72%and 0.17%respectively.There was a significant difference in the distribution of fast metabolic genotype between the two nationalities(P<0.001).There were significant differences in the distribution of the medium and slow metabolism genotypes in the two ethnic groups(P<0.001).The comparison of non ST segment elevation and ST segment elevation ACS was statistically significant(P<0.05).When we do case-control studies.The interaction between the history of diabetes,slow and metabolism CYP2C19 genotype,fasting blood glucose,low density lipoprotein,platelet-to-lymphocyte ratio and the interaction of CYP2C19 with cholesterol are relative risk factor of acute coronary syndrome.(3)The distribution frequencies of three genotypes of rs738409 CC,CG and GG were14.03%,15.02%,7.10%in Uygur group,and 24.75%,29.21%and 9.90%in the Han nationality.The patients with acute coronary syndrome were 36.21%,45.52%and 18.27%,and 41.31%,42.95%and 15.74%in the control group.Single factor Logistic regression analysis showed that the rs738409 gene locus genotype on the occurrence of acute coronary syndrome were not correlated(P>0.05),multivariate logistic regression analysis showed that hypertension,body mass index(BMI),fasting blood glucose(FBG),three glycerol ester(TG),low density lipoprotein,PLR is the leading cause of acute coronary syndrome risk factors,and there are no correlation between rs738409 polymorphism and acute coronary syndrome(P=0.646),but rs738409 polymorphism with BMI and triglyceride on the occurrence and development of acute coronary syndrome in interaction.Conclusions:(1)Elevated PLR is found to be a predictor of all-cause mortality and cardiovascular events.(2)The distribution of CYP2C19 genotypes of Han and Uygur ACS patients in Xinjiang area is quite different.The Uygur population in fast metabolizing genotype is higher than that in Han nationality.(3)The risk factors for acute coronary syndrome are diabetes history,slow metabolism genotype in CYP2C19,fasting blood glucose,low density lipoprotein,platelet lymphocyte ratio,CYP2C19 and cholesterol interaction.(4)PNPLA3 gene rs738409 polymorphism and acute coronary syndrome is not related,but there are interaction between genes and BMI,triglycerides with acute coronary syndrome,platelet to lymphocyte ratio is risk factors of acute coronary syndrome,high platelet-to-lymphocyte ratio was 1.016 times than lower platelet-to-lymphocyte ratio in the risk of acute coronary syndrome.
Keywords/Search Tags:Platelet-to-lymphocyte ratio, Acute coronary syndrome, CYP2C19gene polymorphism, PNPLA3 gene, Rs738409 polymorphism
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