醛固酮合成酶基因多型性與台灣瓣膜性心臟病患者之相關性

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Title:	醛固酮合成酶基因多型性與台灣瓣膜性心臟病患者之相關性 The Association Between Aldosterone Synthase (CYP11B2) Gene Polymorphism and Valvular Heart Disease in Taiwanese
Authors:	莊曜聰 Yao-Tsung,Chuang
Contributors:	中山醫學大學;醫學院;醫學研究所;楊順發;翁國昌
Keywords:	基因多型性;礦物類皮質激素受器;醛固酮合成酶;瓣膜性心臟病 Polymorphism;aldosterone synthase (CYP11B2) gene;mineralocorticoid receptor;valvular hear disease
Date:	2011
Issue Date:	2011-10-25T07:32:02Z (UTC)
Abstract:	中文摘要研究背景鬱血性心臟衰竭(congestive heart failure)是六十五歲以上老年人需要住院之主因之一。造成鬱血性心臟衰竭的主要原因包括心肌梗塞、其他型態之缺血性心臟病、高血壓、瓣膜性心臟病及心肌病變。醛固酮的活性可能在鬱血性心臟衰竭的進程中扮演著重要的角色。刺激心肌細胞中的醛固酮受體會促進細胞死亡(apoptosis)，導致心肌纖維化及心室再朔造(ventricular remodeling)。醛固酮是作用於腎素-血管張力(renin-angiotensin system)系統的主要作用物質之一。醛固酮最顯著的作用特徵為藉由增加遠端腎元對鈉離子的在吸收，因而增加血管內容積。醛固酮的分泌主要是由醛固酮合成酶所調節；醛固酮合成酶的濃度又與其合成酶的基因表現相關。人類的醛固酮合成酶基因(CYP11B2)位於第八對染色體(8q22), 與11-β羥化酶基因(CYP11B1)位置相近. 醛固酮合成酶基因(CYP11B2)的變異性已經證實與多重新血管疾病相關；例如高血壓、心房顫動、急性心肌梗塞、冠狀動脈疾病及鬱血性心臟衰竭。然而，瓣膜性心臟病是造成鬱血性心臟衰竭的主因之一。回顧過去文獻，並沒有評估腎素-血管張力素(renin-angiotensin system)系統基因多型性與瓣膜性心臟病之相關性之研究。所以在此研究中我們假設醛固酮合成酶基因(CYP11B2)的多型性與瓣膜性心臟病有相關性。研究方法從704個選定的受試者中進行臨床檢查及檢驗，包括詢問病史，理學檢查，抽血檢查，休息時的12導程心電圖和心臟超音波檢查。把受試者分為瓣膜性心臟病及非瓣膜性心臟病兩組。並從週邊血液中抽取DNA，進行聚合酵素連鎖反應（polymerase chain reaction- restriction fragment length polymorphism analysis），分析礦物類皮質激素結受器基因於G3514C、A4582C和醛固酮合成酶基因（CYP11B2）於T-344C段的基因多型性，並且根據心臟超音波測量數據和性別進行統計分析。研究結果在本研究中總共704受試者中，有109 病人有瓣膜性心臟病；其他595個病人沒有瓣膜性心臟病。我們選用三種多型態基因，包括礦物質皮質素受器基因A4582C，礦物質皮質素受器基因G3514C，以及醛固酮合成酶(CYP11B2)基因。礦物質皮質素受器基因A4582C和礦物質皮質素受器基因G3514C之基因多型性在兩族群及性別間並無相關性。另外，醛固酮合成酶(CYP11B2)基因之多型性在瓣膜性心臟病族群與非瓣膜性心臟病族群並無顯示統計學上之意義。在女性病人(n=217)中，醛固酮合成酶(CYP11B2)基因之多型性則在兩族群中顯示統計學上之意義。在女性非瓣膜性心臟病族群中，有101 個病人(58.7%)有T/T 基因型；59個病人(34.3%)有T/C基因型及12個病人(7.0%)有C/C基因型 (T/T:T/C+C/C:101人 (58.7%):71人(41.3%).)。在女性瓣膜性心臟病族群中，有17個病人(37.8%)有T/T 基因型；26個病人(57.8%)有T/C基因型及2個病人(4.4%)有C/C基因型(T/T:T/C+C/C: 17 patients (37.8%):28 patients (62.2%).) 。在女性非瓣膜性心臟病族群中，醛固酮合成酶(CYP11B2)基因之多型性與左心房直徑及左心室質量之相關性可顯示出統計學上之意義。在女性非瓣膜性心臟病族群中，左心房直徑在T/T 族群為35.67 ± 6.47mm ；於T/C族群為38.09 ± 5.24mm(p=0.038)。左心室質量在T/T 族群為194.09 ± 39.29 gm；在C/C族群為240.20 ± 49.81 gm ; (p=0.0005)。在女性瓣膜性心臟病族群中，醛固酮合成酶(CYP11B2)基因之多型性與左心房直徑及左心室質量之相關性沒有顯示出統計學上之意義。結論醛固酮合成酶(CYP11B2)基因之多型性與女性瓣膜性心臟病患者具相關性；帶有C基因形的女性患者有較高比例的瓣膜性心臟病。. 醛固酮合成酶(CYP11B2)基因之多型性在瓣膜性心臟病的女性中，與其左心室質量(LVM)有強烈相關性；帶有C基因型的女性患者有較重的左心室質量。關鍵字：基因多型性;礦物類皮質激素受器;醛固酮合成酶;瓣膜性心臟病。 the renal enzyme required for its biosynthesis, aldosterone synthase (CYP11B2). aldosterone synthase (CYP11B2) polymorphisms had been confirmed that effect multiple cardiovascular diseases such as hypertension, atrial fibrillation, acute myocardial infarction, coronary artery disease and congestive heart failure. Valvular heart disease is one of the major cause of congestive heart failure. But no previous study has assessed the genetic aspects of renin-angiotensin system gene polymorphisms in relation to valvular heart disease. We hypothesis that aldosterone synthase (CYP11B2) polymorphisms may associated with valvular heart disease. Methods Total 704 patients were included. All patients underwent a thorough clinical workup, including history taking , physical examination , blood sample examination, 12-lead electrocardiography at rest, and echocardiography examination. They Genomic DNA extracted from peripheral blood samples was subjected to polymerase chain reaction-restriction fragment length polymorphism analysis for the mineralocorticoid receptor loci, G3514C and A4582C, and CYP11B2 T-344C. The genetic distribution of these genes and the association with echocardiographic measurements were statistically analyzed. Result 109 patients have valvular heart disease and the other 595 patients do not have valvular heart disease. We chose three polymorphic genes, including MR A4582C, MR G3514C, CYP11B2.(Table 2) summarizes the gene polymorphisms in VHD-positive group and VHD-negative group. MR A4582C and MR G3514C gene polymorphisms did not show the association on between those two group. In female patients(n=217), there is statistical significance in the CYP11B2 gene polymorphisms between VHD-positive group and VHD-negative group(p: P=0.016;p=0.012) there is statistical significance in the LAD and LVM in the female VHD negative group. In female VHD –negative patients , the LAD is T/T vs T/C: 35.67 ± 6.47 vs 38.09 ± 5.24; p=0.038; the LVM is T/T vs C/C: 194.09 ± 39.29 vs240.20 ± 49.81; p=0.0005 Conclusion Aldosterone Synthase (CYP11B2) Gene Polymorphism associated with female Patients With Valvular heart disease .Genetic variations of the aldosterone synthase (CYP11B2) gene strongly affect left ventricular size and mass in female adults free of valve heart disease. Key words: Polymorphism; aldosterone synthase (CYP11B2) gene; mineralocorticoid receptor; valvular hear disease.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/4226
Appears in Collections:	[醫學研究所] 博碩士論文

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