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Investigation of Renalase gene rs2576178 polymorphism in patients with coronary artery disease.

ABSTRACT: Renalase gene rs2576178 polymorphism has been demonstrated to be a risk factor of ischemic stroke, essential hypertension, and end-stage renal disease, but the association Renalase with risk of coronary artery disease (CAD) has been less reported. Therefore, we detected Renalase rs2576178 polymorphism in 449 CAD patients and 507 healthy controls using matrix-assisted laser-desorption ionization (MALDI)/time of flight (TOF)-mass spectrometry (MS). It was found that GG genotype or G allele of rs2576178 polymorphism was associated with the risk of CAD. Stratified analysis indicated that Renalase polymorphism significantly increased the risk of CAD in females, smokers, and alcoholics. However, there was no significant association between different genotypes of rs2576178 polymorphism and clinical parameters. In summary, Renalase rs2576178 polymorphism is associated with increased risk of CAD, but this finding should be confirmed by larger studies with more diverse ethnic populations.

SUBMITTER: Hu N

PROVIDER: S-EPMC6137248 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Investigation of Renalase gene rs2576178 polymorphism in patients with coronary artery disease.

Hu Ning N Wang Jun J Hu Pengfei P Li Zhongmei Z

Bioscience reports 20180913 5

Renalase gene rs2576178 polymorphism has been demonstrated to be a risk factor of ischemic stroke, essential hypertension, and end-stage renal disease, but the association Renalase with risk of coronary artery disease (CAD) has been less reported. Therefore, we detected Renalase rs2576178 polymorphism in 449 CAD patients and 507 healthy controls using matrix-assisted laser-desorption ionization (MALDI)/time of flight (TOF)-mass spectrometry (MS). It was found that GG genotype or G allele of rs25 ...[more]

PMID: 30181378

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Project description:BackgroundData 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.MethodsA 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.ResultsVariant 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.ConclusionsIn 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.

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.

Dataset Information

Investigation of Renalase gene rs2576178 polymorphism in patients with coronary artery disease.

Publications

Investigation of Renalase gene rs2576178 polymorphism in patients with coronary artery disease.

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