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Susceptible gene polymorphism in patients with three-vessel coronary artery disease.

ABSTRACT: BACKGROUND:Data of susceptible gene polymorphisms related to progression of coronary atherosclerosis in patients with three-vessel disease (TVD) is limited in China. This case-control study aimed to analyze the differences of variant carrier frequencies between cases and controls, and to explain the possible genetic effects on the progression of TVD. METHODS:A total of 8943 TVD patients were consecutively enrolled. Major adverse cardiac and cerebrovascular events (MACCE) included all-cause death, acute myocardial infarction, repeat revascularization, readmission and stroke. Patients with 1-year MACCE in this cohort were selected as MACCE group. Blood samples from MACCE group and non-CAD control groups were collected, and a deoxyribonucleic acid library was created. A total of 34 tag or hot single nucleotide polymorphisms (SNPs) in six genes including CDKN2B-AS1, ADAMTS7, ABO, ADAMTS13, IL-18, and PECAM1 were analyzed by a SNPscan™ multi-genotyping kit. Carrier frequencies of each SNP were compared between the two groups using dominant, recessive and codominant allele model, respectively. Multivariate logistic regression model was established. RESULTS:Variant allele frequencies of rs10757274, rs1333042, rs1333049, rs4977574, rs9632884, rs1063192 and rs3217986 on CDKN2B-AS1 gene showed significant differences between the two groups in at least one allele model. Variant allele frequency of rs3217986 was not statistically significant after adjusting for the false discovery rate using Benjamini-Hochberg procedure (Q?>?0.05). Variant allele frequencies of rs1333049, rs10757274, rs4977574 on CDKN2B-AS1 gene were significantly higher in MACCE group in all dominant, recessive and codominant models. Rs1055432 on ADAMTS13 and rs8176694 on ABO gene showed threshold significance between the two groups. After multivariable adjustment, G mutant homozygous rs9632884 (GG vs. GC?+?CC) (OR: 0.24; 95% CI: 0.09-0.65; P?=?0.005) on CDKN2B-AS1 gene were independent protective factor of MACCE in recessive model. CONCLUSIONS:In patients with TVD in China, variant alleles on CDKN2B-AS1 gene may form part of the genetic basis of coronary atherosclerosis progression, promoting or suppressing ischemic events.

SUBMITTER: Liu R

PROVIDER: S-EPMC7161109 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Susceptible gene polymorphism in patients with three-vessel coronary artery disease.

Liu Ru R Song Lei L Jiang Lin L Tang Xiaofang X Xu Lianjun L Gao Zhan Z Zhao Xueyan X Xu Jingjing J Gao Runlin R Yuan Jinqing J

BMC cardiovascular disorders 20200415 1

<h4>Background</h4>Data of susceptible gene polymorphisms related to progression of coronary atherosclerosis in patients with three-vessel disease (TVD) is limited in China. This case-control study aimed to analyze the differences of variant carrier frequencies between cases and controls, and to explain the possible genetic effects on the progression of TVD.<h4>Methods</h4>A total of 8943 TVD patients were consecutively enrolled. Major adverse cardiac and cerebrovascular events (MACCE) included ...[more]

PMID: 32293292

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Project description:Coronary artery disease (CAD) is a disease in which a waxy substance called plaque builds up inside the coronary arteries. Apelin is a novel endogenous peptide with inotropic and vasodilatory properties and is the ligand for the angiotensin receptor-like 1 (APJ) receptor. We aimed to determine genotype and allele frequencies of APJ receptor A445C gene polymorphism in Turkish patients with CAD and healthy controls by RFLP-PCR. This study was performed on 159 unrelated CAD patients and 62 healthy controls. We obtained AA, AC and CC genotype frequencies in CAD patients as 41.5%, 49.1% and 9.4%, respectively. In the control group, frequencies of genotypes were found as 35.5% for AA, 48.4% for AC and 16.1% for CC. We did not observe difference in APJ receptor A445C polymorphism between CAD patients and healthy controls (?(2) = 2.178; df = 2; P = 0.336). The A allele was encountered in 66% (210) of the CAD and 59.7% (74) of the controls. The C allele was seen in 34% (108) of the CAD and 40.3% (50) of the controls. Allele frequencies of interested genes were not significantly different between groups (?(2) = 1.57; df = 1; p = 0.225). The frequencies of APJ receptor A445C genotype were not significantly different between control and patients. None of the three APJ receptor A445C genotypes, AA, AC and CC displayed significant difference in CAD patients. We did not find any difference in the clinical parameters except for weight and diastolic blood pressure levels in the AA, AC and CC genotypes of patients. Individuals with CC genotypes had significantly higher weight, systolic and diastolic blood pressure levels and systolic blood pressure than other genotypes, P ? 0.05. In addition, HDL-C level was found decreased, but this reduction was not statistically significant. Contrarily, the low levels of weight, SBP, DBP and TC were statistically significant in the subjects with AA genotype in CAD. In conclusion, CC genotype carriers may have more risk than other genotypes in the development of hypertension in CAD, but not AAgenotype carriers. We suggest that this polymorphism may not be a marker of CAD, but it may cause useful in function of the apelin/APJ system and may be a genetic predisposing factor for diagnostic processes and can be helpfull in finding new treatment strategies. We think that it is required to further comprehensive studies in order to make clear this situation in CAD.

Project description:AimThe aim of this study was to compare long-term all-cause mortality between patients receiving percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) using multiple (MAG) or single arterial grafting (SAG).Methods and resultsThe current study is a post hoc analysis of the SYNTAX Extended Survival Study, which compared PCI with CABG in patients with three-vessel (3VD) and/or left main coronary artery disease (LMCAD) and evaluated survival with ≥10 years of follow-up. The primary endpoint was all-cause mortality at maximum follow-up (median 11.9 years) assessed in the as-treated population. Of the 1743 patients, 901 (51.7%) underwent PCI, 532 (30.5%) received SAG, and 310 (17.8%) had MAG. At maximum follow-up, all-cause death occurred in 305 (33.9%), 175 (32.9%), and 70 (22.6%) patients in the PCI, SAG, and MAG groups, respectively (P < 0.001). Multiple arterial grafting [adjusted hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.49-0.89], but not SAG (adjusted HR 0.83, 95% CI 0.67-1.03), was associated with significantly lower all-cause mortality compared with PCI. In patients with 3VD, both MAG (adjusted HR 0.55, 95% CI 0.37-0.81) and SAG (adjusted HR 0.68, 95% CI 0.50-0.91) were associated with significantly lower mortality than PCI, whereas in LMCAD patients, no significant differences between PCI and MAG (adjusted HR 0.90, 95% CI 0.56-1.46) or SAG (adjusted HR 1.11, 95% CI 0.81-1.53) were observed. In patients with revascularization of all three major myocardial territories, a positive correlation was observed between the number of myocardial territories receiving arterial grafts and survival (Ptrend = 0.003).ConclusionOur findings suggest that MAG might be the more desirable configuration for CABG to achieve lower long-term all-cause mortality than PCI in patients with 3VD and/or LMCAD.Trial registrationRegistered on clinicaltrial.gov. SYNTAXES: NCT03417050 (https://clinicaltrials.gov/ct2/show/NCT03417050); SYNTAX: NCT00114972 (https://www.clinicaltrials.gov/ct2/show/NCT00114972).

Dataset Information

Susceptible gene polymorphism in patients with three-vessel coronary artery disease.

Publications

Susceptible gene polymorphism in patients with three-vessel coronary artery disease.

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