Wang Pengyun, Xu Chengqi, Wang Chuchu, Wu Yanxia, Wang Dan, Chen Shanshan, Zhao Yuanyuan, Wang Xiaojing, Li Sisi, Yang Qin, Zeng Qiutang, Tu Xin, Liao Yuhua, Wang Qing K, Cheng Xiang
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
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.
PLoS One. 2015 May 19;10(5):e0125926. doi: 10.1371/journal.pone.0125926. eCollection 2015.
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.
心力衰竭影响着全球1%至2%的成年人口，冠状动脉疾病（CAD）是70%患者心力衰竭的潜在病因。在动物模型中，apelin及其apelin受体（APJ）通路与心力衰竭的发病机制有关，但在人类中是否有类似作用尚不清楚。我们研究了位于5'-非翻译区的一个功能变异rs9943582（-154G/A），该变异在一个由1751例CAD病例和1022例对照组成的人群中与APJ受体基因（APLNR）表达降低有关。变异rs9943582与CAD无关，但在CAD患者中，它与左心室收缩功能障碍显著相关（431例左心室收缩功能障碍的CAD患者（左心室射血分数或LVEF<40%）与1046例无左心室收缩功能障碍的CAD患者（LVEF>50%）相比（P校正=6.71×10-5，OR=1.43，95%CI，1.20-1.70）。此外，rs9943582还与定量超声心动图参数显著相关，包括左心室舒张末期直径（效应大小：每个风险等位基因A增加1.67±0.43mm，P=1.15×10-4）、左心房大小（效应大小：每个风险等位基因A增加2.12±0.61mm，P=9.56×10-4）和LVEF（效应大小：每个风险等位基因A降低2.59±0.32%，P=7.50×10-15）。我们的研究结果表明，rs9943582的等位基因A与CAD人群中的左心室收缩功能障碍、左心室舒张末期直径、左心房直径和LVEF显著相关，这表明apelin/APJ系统在与缺血性心脏病相关的心力衰竭病理中起重要作用。
