| Summary: | 碩士 === 國立臺灣大學 === 臨床醫學研究所 === 96 === Introduction: Considering the fundamental role of neurohormonal factors in the pathophysiology of systolic heart failure (sHF), variants of genes involved in the renin angiotensin system (RAS) are logical candidates. The objective of this study is to identify possible genetic polymorphisms of patients experiencing sHF.
Methods: A total of 123 patients with sHF (clinical symptoms and left ventricle ejection fraction < 45%) and 386 patients with good left ventricular (LV) contractility (ejection fraction >60%) were enrolled into this study. A non-parsimonious multivariable logistic regression model that incorporated potential risk factors was applied to calculate the propensity score for developing sHF. A 1:1 case-control selection process was made according to the rank of propensity. Seven genetic polymorphisms were then identified: T174M, M235T, G-6A, A-20C, G-152A, G-217A, and ACE I/D.
Results: Ninety-three patients (68 men and 25 women, age: 60+/-14) with sHF were enrolled. These patients were well-matched with 93 control subjects (71 men and 22 women, age: 62+/-12) relating to age, sex, presence of coronary heart disease, previous myocardial infarction, hypertension, diabetes mellitus, serum levels of high- and low-density lipoprotein cholesterol, triglycerides, and LV mass to serve as a control. T174M CC genotype was positively associated with sHF (OR: 2.81, 95% CI: 1.20 to 6.61, p=0.018). G-152A GG genotype was also positively associated with the presence of sHF (OR: 6.25, 95% CI 1.54 to 25.4, p=0.010). OR of ACE DD genotype for sHF, as compared with ACE II genotype was 1.37 (p=0.475), and OR for ID genotype compared with II genotype was 5.95 for sHF (95% CI: 2.16 to 16.4, p=0.001). Further classification through a multiple partitioning tree did not find any interaction among these polymorphisms.
Conclusions: Polymorphisms of the RAS may play an important role in the pathogenesis of sHF. Exploration of these RAS genes related to sHF by means of a well-matched case-control study may provide more targeted and tailored treatment of systolic heart failure.
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