Association of SNP Rs9943582 in APLNR with Left Ventricle Systolic Dysfunction in Patients with Coronary Artery Disease in a Chinese Han GeneID Population

Abstract

Heart failure affects 1–2% of the adult population worldwide and coronary artery disease (CAD) is the underlying etiology of heart failure in 70% of the patients. The pathway of apelin and its apelin receptor (APJ) was implicated in the pathogenesis of heart failure in animal models, but a similar role in humans is unknown. We studied a functional variant, rs9943582 (-154G/A), at the 5’-untranslated region, that was associated with decreased expression of the APJ receptor gene (APLNR) in a population consisting of 1,751 CAD cases and 1,022 controls. Variant rs9943582 was not associated with CAD, but among CAD patients, it showed significant association with left ventricular systolic dysfunction (431 CAD patients with left ventricular systolic dysfunction (LV ejection fraction or LVEF< 40%) versus 1,046 CAD patients without LV systolic dysfunction (LVEF>50%) (P-adj = 6.71×10-5, OR = 1.43, 95% CI, 1.20–1.70). Moreover, rs9943582 also showed significant association with quantitative echocardiographic parameters, including left ventricular end-diastolic diameter (effect size: increased 1.67±0.43 mm per risk allele A, P = 1.15×10-4), left atrial size (effect size: increased 2.12±0.61 mm per risk allele A, P = 9.56×10-4) and LVEF (effect size: decreased 2.59±0.32 percent per risk allele A, P = 7.50×10-15). Our findings demonstrate that allele A of rs9943582 was significantly associated with left ventricular systolic dysfunction, left ventricular end-diastolic diameter, the left atrial diameter and LVEF in the CAD population, which suggests an important role of the apelin/APJ system in the pathology of heart failure associated with ischemic heart disease.

Association of apelin and apelin receptor with the risk of coronary artery disease: a meta-analysis of observational studies

“…Table 2A and 2B jointly show the baseline characteristics of 3 articles that assessed the association of APLNR gene rs9943582 polymorphism with CAD risk [ 24 – 26 ]. As 1 study provided the results by sex [ 25 ], 1 study by both sex and blood pressure [ 26 ] and 1 study by both ethnicity and CAD subtype [ 24 ], there were 10 studies in pooled analysis, including 5975 CAD patients and 4717 controls. Year of publication ranged from 2009 to 2015.…”

Meta-Analysis on the Correlation Between APOM rs805296 Polymorphism and Risk of Coronary Artery Disease

“…In recent years, accumulating evidence indicates that genetic polymorphisms may be implicated in individual susceptibility to CAD, including polymorphisms within genes of APLNR [ 8 ], interleukin-6 [ 9 ], CYP7A1 [ 10 ], and PAI-1 [ 11 ]. In addition, the apolipoprotein M gene ( ApoM ), located on human chromosome 6 p21.31, has been reported to be significantly related to the occurrence of CAD [ 12 ].…”

Lack of association between the APLNR variant rs9943582 with ischemic stroke in the Chinese Han GeneID population

“…Previous functional research identified an association between the apelin receptor and apelin with atherosclerosis [ 23 ]. However, no genetic associations between rs9943582 and coronary artery disease, which shares a similar pathogenic mechanism to that of stroke, were identified in our previous study of Chinese individuals or in research by Kunihiko et al into Japanese and Korean populations [ 24 – 25 ]. Similarly, our present case–control association analysis detected no allelic or genotypic association between rs9943582 and ischemic stroke in the Chinese Han GeneID population, although the study population provided sufficient statistical power.…”

“…The subjects in the present case–control genetic association study were enrolled from the GeneID database, which is an ongoing study of the Chinese Han population that has collected >80,000 DNA samples and available clinical data. The GeneID database aims to identify susceptibility genes or other risk factors for cardiovascular and cerebrovascular diseases in the Chinese Han population [ 25 , 27 – 35 ]. This study was approved by the Ethics Committee of Huazhong University of Science and Technology and conforms to the Declaration of Helsinki guidelines.…”