Bienertová-Vasků Julie Anna, Spinarová Lenka, Bienert Petr, Vasků Anna
Institute of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Heart Vessels. 2009 Mar;24(2):131-7. doi: 10.1007/s00380-008-1090-5. Epub 2009 Apr 1.
Patients with chronic heart failure (CHF) express enhanced catabolic metabolism finally resulting in overall weight loss, whereas adipokines might play a crucial role in signaling among tissues. The aim of this study was to investigate the possible associations of defined variability in leptin (dbSNP ID rs7799039), proopiomelanocortin (dbSNP ID rs3754860 and dbSNP ID rs1009388), and leptin receptor gene (dbSNP rs1137101) with CHF and evaluate their potential as the CHF susceptibility genes. The case-control study comprised a total of 372 patients of Caucasian origin with chronic heart failure (New York Heart Association [NYHA] functional classes II-IV, ejection fraction (EF) <40%) and 407 healthy controls. They were genotyped for the leptin (LEP) -2548 G/A, leptin receptor (LEPR) Gln223Arg, and proopiomelanocortin (POMC) RsaI (5'-untranslated region) and C1032G variants (intron 1) using PCR-based methodology. No case-control differences in genotype as well as allele frequencies were observed between CHF patients and controls. We constructed POMC RsaI/C1032G haplotypes, having found no significant association with body mass index (BMI), left ventricle ejection fraction (LVEF), left ventricle hypertrophy (LVH) and diabetes mellitus (DM). Multivariate regression analyses revealed an approximately 2-fold risk for NYHA class IV associated with the LEPR Gln223Arg (P = 0.0000001, odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.56-2.84); it also displayed an independent prediction role for LVEF in heart failure cases of all etiologies (P = 0.002, OR = 4.05, 95% CI = 1.36-10.06). In subanalyses according to CHF etiology the LEPR Gln223Arg showed an independent prediction role for NYHA IV in IHD patients (P = 0.0001, OR = 2.50, 95% CI = 1.69-3.82) and both for NYHA IV(P = 0.007, OR = 2.04, 95% CI = 1.20-3.84) and LVEF (P = 0.004, OR = 11.87, 95% CI = 2.08-55.6) in DCMP patients. The role of the polymorphic variants in the genes encoding for adipokines as potential CHF susceptibility genes is unclear. Based on our findings, the LEPR Gln223Arg polymorphism could be considered a disease susceptibility modulating factor both in ischemic heart disease or dilated cardiomyopathy patients.
慢性心力衰竭（CHF）患者表现出分解代谢增强，最终导致总体体重减轻，而脂肪因子可能在组织间信号传导中起关键作用。本研究的目的是调查瘦素（dbSNP ID rs7799039）、阿黑皮素原（dbSNP ID rs3754860和dbSNP ID rs1009388）以及瘦素受体基因（dbSNP rs1137101）的特定变异与CHF之间可能存在的关联，并评估它们作为CHF易感基因的潜力。病例对照研究共纳入了372名白种人慢性心力衰竭患者（纽约心脏协会[NYHA]心功能分级II-IV级，射血分数[EF]<40%）和407名健康对照。采用基于PCR的方法对瘦素（LEP）-2548 G/A、瘦素受体（LEPR）Gln223Arg以及阿黑皮素原（POMC）RsaI（5'-非翻译区）和C1032G变异（内含子1）进行基因分型。CHF患者与对照组之间在基因型以及等位基因频率上未观察到病例对照差异。我们构建了POMC RsaI/C1032G单倍型，发现其与体重指数（BMI）、左心室射血分数（LVEF）、左心室肥厚（LVH）和糖尿病（DM）无显著关联。多因素回归分析显示，与LEPR Gln223Arg相关的NYHA IV级风险增加约2倍（P = 0.0000001，比值比[OR]=2.10，95%置信区间[CI]=1.56 - 2.84）；它在所有病因的心力衰竭病例中对LVEF也显示出独立预测作用（P = 0.002，OR = 4.05，95% CI = 1.36 - 10.06）。在根据CHF病因进行的亚分析中，LEPR Gln223Arg在缺血性心脏病（IHD）患者中对NYHA IV级显示出独立预测作用（P = 0.0001，OR = 2.50，95% CI = 1.69 - 3.82），在扩张型心肌病（DCMP）患者中对NYHA IV级（P = 0.007，OR = 2.04，95% CI = 1.20 - 3.84）和LVEF（P = 0.004，OR = 11.87，95% CI = 2.08 - 55.6）均显示出独立预测作用。脂肪因子编码基因中的多态性变异作为潜在CHF易感基因的作用尚不清楚。基于我们的研究结果，LEPR Gln223Arg多态性可被视为缺血性心脏病或扩张型心肌病患者疾病易感性的调节因子。
