腎素-血管張力素系統基因多形性與非瓣膜性心臟衰竭之關聯性研究

Association Study of Genetic Polymorphisms of the Renin-Angiotensin-System & non-valvular Systolic Heart Failure

張勝南(Sheng-Nan Chang)

指導教授 ： 江福田

國立臺灣大學/醫學院/臨床醫學研究所/碩士(2008年)

https://doi.org/10.6342/NTU.2008.00559

摘要

簡介:
從心臟衰竭的病態生理學來看‚牽涉在其中的神經荷爾蒙機制都會跟心臟衰竭的產生有所關聯。在這當中‚跟腎素-血管張力素系統有關的基因變化都有可能是會引發心臟衰竭的候選基因。這個研究的目的是要找出那些基因的多形性會引起病人的心臟衰竭。
方法:
總共有123名心臟衰竭的病患 (有臨床症狀以及左心室的射出率小於45%),以及386名心臟收縮功能正常的受試者參與這次的研究。經由非簡約分析的多變數羅吉斯迴歸分析(non-parsimonious multivariable logistic regression)去估算全部受試者的propensity score。然後再依據受試者的propensity score加以分為實驗組還有對照組,然後分析這些受試者的基因多形性。在這個研究總夠探討T174M, M235T, G6-A, A-20C, G-152A, G-217A, 以及ACEI/D等七個基因多形性。

結果:
總共有93組配對完整的受試組接受最後的分析。配對的病患組還有對照組不管在年齡、性別、冠狀動脈疾病、心肌梗塞病史、高血壓、糖尿病、血中血脂濃度以及左心室質量等條件都沒有統計學上的差別。分析的結果發現到T174M CC跟心臟衰竭的產生有正相關(OR: 2.81, 95% CI: 1.20 to 6.61, p=0.018)。G-152A GG也會跟心臟衰竭的產生有正相關(OR: 6.25, 95% CI 1.54 to 25.4, p=0.010)。至於ACE I/D方面, ACE DD基因型跟ACE ID基因型相比之下有呈現正相關的趨勢但是並沒沒有統計學上面的差別(OR: 1.37, p=0.475)。ACE ID基因型跟ACE II基因型相比則有較大的機會會產生心臟衰竭(OR: 5.95, 95% CI: 2.16 to 16.4, p=0.001)。經由multiple partitioning tree的分析發現這些基因多形性並不會有交互作用的影響。

結論:
腎素-血管張力素系統的基因多形性有可能在心臟衰竭的發生過程中扮演重要的角色。經由這個配對完整的研究來探討腎素-血管張力素系統的基因多形性跟心臟衰竭的關係可以對於未來心臟衰竭的治療可以提供更加完整以及適切的治療。

關鍵字

腎素-血管張力素系統 ； 基因 ； 心血管疾病 ； 心臟衰竭

並列摘要

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.

並列關鍵字

Renin-angiotensin system ； genetics ； cardiovascular disease ； heart failure

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