アルファ-アドゥチンと塩への過敏性のポリモルフィズムが,エッセンシャル高血圧の患者に見られる
D Cusi1, C Barlassina, T Azzani
1Postgraduate School of Nephrology, University of Milan, Italy.
Lancet (London, England)
|May 10, 1997
まとめ
特定のアルファ-アドゥチン遺伝子変異 (Gly 460 Trp) は,本質的な高血圧に関連しています. この変異を持つ個人は,塩への感受性が高まり,利尿剤治療に対する反応が良くなります.
科学分野:
- 遺伝学 遺伝学とは
- ネフロロジーはネフロロジーを用います.
- 心血管医学 心血管医学
背景:
- 腎上でのナトリウム輸送の異常は高血圧に関連しています.
- 腎管のタンパク質であるアドツチンは,アクチン細胞骨格を通してイオン輸送を調節すると仮定されています.
研究 の 目的:
- アルファ-アドゥチン遺伝子多形態 (Gly 460 Trp) とエッセンシャル高血圧との関連を調査する.
- このポリモルフィズムが,ナトリウムバランスの変化に対する血圧反応に与える影響を評価する.
主な方法:
- アルファ-アドゥチンの位置付近のDNAマーカーを用いて,高血圧の137組の兄弟同士の結合分析.
- アルファ-アドゥチンの多形性について,高血圧患者477人,高血圧患者322人の遺伝子型決定を行った.
- 460 Trp アレルを持つ,または持たない高血圧患者の塩分感受性 (急性および慢性) 検査.
主要な成果:
- アルファ-アドゥチンロカスマーカーとエッセンシャル高血圧との間に有意な関連性が見られた.
- 460 Trp変異と高血圧 (p = 0.0003) の間に有意な関連性が見つかりました.
- 変異性アレル (Gly/Trp) を有する患者は,野生型ホモジゴトと比較して,ナトリウム変化とヒドロクロロチアジド治療に反応して,より大きな血圧低下を示した (p = 0.001とp = 0.002,それぞれ).
結論:
- アルファ-アドゥチンの位置は,本質的な高血圧と有意に結びついています.
- Gly 460 Trpの多形性は,塩分に敏感な精性高血圧と関連しています.
- この多形性は,利尿療法やナトリウム減少戦略から恩恵を受ける高血圧患者を特定するのに役立ちます.
さらに関連する動画
関連する概念動画
Hormonal Regulation
The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
Adrenergic Receptors: ɑ Subtype
Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
Hypertension and Regulation of Blood Pressure
Hypertension, the most common cardiovascular disease, is diagnosed through repeated measurements of elevated blood pressure. Its risks, including damage to the kidney, heart, and brain, are directly proportional to blood pressure levels. Starting from 115/75 mm Hg, the risk of cardiovascular disease doubles with each increment of 20/10 mm Hg. The diagnosis relies on blood pressure measurements, not on patient symptoms, as hypertension is often asymptomatic until end-organ damage is imminent or...
Antihypertensive Drugs: Potassium-Sparing Diuretics
Liddle syndrome is a genetically inherited form of hypertension characterized by the overactivity of epithelial sodium channels in the nephron, the functional unit of the kidney. This heightened activity leads to increased sodium reabsorption and excessive excretion of potassium. To counteract this, potassium-sparing diuretics such as amiloride are used. They function by blocking these sodium channels, thereby reducing the influx of sodium into the epithelial cells and minimizing the loss of...
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
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...


