title: 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.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Pengyun
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research and Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Chengqi
authors.initials: C
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research and Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Chuchu
authors.initials: C
authors.lastname: Wang
authors.affiliation: The First Hospital of Wuhan City, Wuhan, P. R. China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research and Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research and Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research and Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research and Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research and Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Sisi
authors.initials: S
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research and Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Qiutang
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research and Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tu
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research and Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, P. R. China; Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, and Department of Molecular Medicine, Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, United States of America.
authors.forename: Qing K
authors.initials: QK
authors.lastname: Wang
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cheng
mesh_terms: D000368:Aged; D000075244:Apelin Receptors; D016022:Case-Control Studies; D002681:China; D003324:Coronary Artery Disease / Q000235:genetics / Q000503:physiopathology*; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000235:genetics*
chemical_list: C104575:APLNR protein, human; D000075244:Apelin Receptors; D043562:Receptors, G-Protein-Coupled