Validation of the association between AGTRL1 polymorphism and coronary artery disease in the Japanese and Korean populations

Abstract

Coronary artery disease (CAD) and stroke are the major health problems in many countries because of their increasing prevalence and high mortality. It is well known that CAD and stroke are based on atherosclerosis and shared environmental and genetic risk factors. Recently, an association of a functional sequence variation À154G4A in the angiotensin receptor-like 1 (AGTRL1) with a susceptibility to stroke was reported. In this study, we investigated a total of 1479 CAD cases and 2062 controls from the Japanese and Korean populations to validate the association of AGTRL1 with CAD. However, we obtained no evidence of the association in both the Japanese (odds ratio (OR)¼0.95, 95% confidence interval (CI); 0.82-1.10, P¼0.47, allele count model) and Korean (OR¼0.90, 95% CI; 0.77-1.05, P¼0.18, allele count model) populations. In addition, there was no trend of association between the risk allele and severity of coronary atherosclerosis. These data suggested that AGTRL1 did not contribute much to the atherosclerosis of the coronary artery. Keywords: coronary artery disease; AGTRL1; single nucleotide polymorphism; case-control study INTRODUCTIONCoronary artery disease (CAD) is caused by the thrombotic occlusion of coronary arteries and becomes a major health problem in many countries. CAD is mainly based on the atherosclerosis of the coronary artery and often manifests with sudden chest pain because of reversible (angina pectoris, AP) or irreversible (myocardial infarction, MI) ischemia in the heart caused by the decreased blood flow in the coronary arteries.Stroke, in particular, ischemic stroke is caused by the thrombotic occlusion of cerebral arteries associated with atherosclerosis, which shares at least in part pathogenic mechanisms and risk factors such as smoking, hypertension, hypercholesterolemia and diabetes mellitus with CAD, 1 and recent genome-wide association studies have identified polymorphism on chromosome 9p21 as a common risk variant for both stroke and CAD. [2][3][4] In addition, Hata et al. 5 recently reported that angiotensin receptor-like 1 (AGTRL1) was highly expressed in the cardiovascular system and the central nervous system and that a functional sequence variation À154G4A (rs9943582) in the 5¢-anking region of AGTRL1 was associated with the stroke in Japanese; the G allele frequencies were 0.721 and 0.666 in patients and controls, respectively (OR¼1.30, 95% CI; 1.14-1.47, P¼6.6Â10 À5 ).

Interactive Association of Five Candidate Polymorphisms in Apelin/APJ Pathway with Coronary Artery Disease among Chinese Hypertensive Patients

“…Moreover, Hinohara and coworkers in the Japanese and Korean populations also failed to observe a positive association between rs9943582 in APJ gene and CAD [23], in agreement with the results of our single-locus analysis. Even though, we cannot rule out the participation of examined polymorphisms in the functional expression of apelin/APJ pathway or CAD, because the estimated low-penetrance haplotype in apelin gene exhibited significant association with CAD risk, which challenges the claim of the common-disease common-variant hypothesis [24].…”

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

“…However, in our case-control association analysis, we did not detect any allelic or genotypic association between rs9943582 and CAD in the Chinese Han GeneID population, although the study population provided sufficient statistical power. Our result is consistent with the study by Hinohara et al, which also showed negative association between rs9943582 and CAD in Japanese and Korean populations [ 35 ].…”

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.…”