Association of natriuretic peptide polymorphisms with left ventricular dysfunction in southern Han Chinese coronary artery disease patients.
BACKGROUND
Left ventricular dysfunction (LVD) occurs with myocardial ischemia and coronary artery disease (CAD). The natriuretic peptide system has compensatory vasodilatory, natriuretic and paracrine effects on LVD and subsequent heart failure. The aim of this study was to investigate the relationship between natriuretic peptide polymorphisms and risk of LVD in CAD patients.


METHODS
We recruited 747 consecutive Southern Han Chinese patients with angiographically confirmed CAD, 201 had a reduced left ventricle ejection fraction (LVEF ≤45%, LVD group) and 546 had a preserved left ventricle ejection fraction (LVEF >45%). The reduced and preserved LVEF groups were matched by gender and age. Taqman assays were performed to identify five polymorphisms in the NPPA-NPPB locus (rs5065, rs5063, rs632793, rs198388 and rs198389).


RESULTS
Single-locus analyses found no significant difference in the allele and genotype frequencies of the reduced and preserved LVEF group, even after adjusting for confounding factors. Subgroup analyses performed by hyperlipidemia (HLP) demonstrated 3 polymorphisms, rs632793 (OR = 0.31, 95% CI 0.1-0.93, P = 0.04), rs198388 (OR = 0.26, 95% CI 0.09-0.79, P = 0.02) and rs198389 (OR = 0.26, 95% CI 0.09-0.80, P = 0.02) were associated with the reduced risk of LVD. No CAD-susceptible haplotypes were identified. Multifactor dimensionality reduction analysis did not detect any gene-to-gene interactions among the five loci. Three loci (rs5063, rs632793 and rs198388) formed the best model with the maximum testing accuracy (39.89%) and cross-validation consistency (10/10).


CONCLUSIONS
Three NPPA-NPPB polymorphisms (rs632793, rs198388 and rs198389) were associated with reduced risk of LVD in CAD patients with HLP.
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Zhijun
Z
Wu
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Min
M
Xu
National Engineering Center for Biochip at Shanghai Shanghai, China.
Haihui
H
Sheng
Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University Shanghai, China.
Yuqing
Y
Lou
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Xiuxiu
X
Su
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Yanjia
Y
Chen
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Lin
L
Lu
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Yan
Y
Liu
Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Wei
W
Jin
D000368:Aged; D044466:Asian People / Q000235:genetics*; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D006949:Hyperlipidemias / Q000208:ethnology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D065840:Protective Factors; D012307:Risk Factors; D013318:Stroke Volume / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control; D016277:Ventricular Function, Left / Q000235:genetics*
C472955:NPPA protein, human; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor
Left ventricular dysfunction; coronary artery disease; heart failure; natriuretic peptide; polymorphism