人間の心臓におけるアニオテンシン変換酵素である. 削除/挿入ポリモルフィズムの影響
A H Danser1, M A Schalekamp, W A Bax
1Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam, COEUR, Erasmus University, Netherlands.
Circulation
|September 15, 1995
まとめ
アンジオテンシン変換酵素 (ACE) 消去ポリモルフィズムは,DD遺伝子型を有する個体において,より高い心動脈ACE活性に関連しています. これは,このACE遺伝子変異と関連した心血管疾患のリスクの増加を説明する可能性がある.
科学分野:
- 心血管遺伝学 心血管遺伝学
- 分子心臓病学 分子心臓病学
背景:
- アンジオテンシン変換酵素 (ACE) 遺伝子挿入/消去 (I/D) ポリモルフィズムが血のACEレベルに影響する.
- この多形性は,心筋梗塞や冠動脈疾患などの心血管疾患に関連しています.
研究 の 目的:
- ACE遺伝子ポリモルフィズムと心臓のACE活性との関係を調査する.
- ACE遺伝子型と心血管疾患のリスクとを結びつける潜在的なメカニズムを探求する.
主な方法:
- 心臓疾患による死亡以外の71人の被験者の心臓のACE活性とACE遺伝子型を決定した.
- 異なるACEゲノタイプ (DD,ID,II) におけるACE活性を分析した.
主要な成果:
- 心臓のACE活動は,DD遺伝子型 (12.7mU/g) の被験者において,ID (8.7mU/g) およびII (9.1mU/g) 遺伝子型 (P < .01) と比較して,有意に高かった.
- この関連性は,性別,年齢,および組織収集時間とは無関係でした.
結論:
- DD遺伝子型は,心臓の最高ACE活動と関連しています.
- 心臓のACE活性が上昇すると,心臓のアンジオテンシンII濃度が上昇し,ACEデレーション多形性と心血管疾患のリスクとの関連が潜在的に根底にある可能性があります.
関連する概念動画
Mutations
Overview
RNA Editing
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Heart Failure II: Pathophysiology
Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...


