帕洛克索纳斯-1作为加勒比海西班牙裔患者用克洛皮多格雷尔治疗的心血管生物标志物:丰富性和功能性
Mariangeli Monero-Paredes1, Ednalise Santiago2, Kelvin Carrasquillo-Carrion2
1Department of Pharmacology and Toxicology, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00936, USA.
International journal of molecular sciences
|October 16, 2024
概括
在加勒比海的西班牙裔患者中,对克洛皮多格雷尔耐药性的帕罗酶-1 (PON1) 活性,而不是丰度,较低. 减少PON1活动可能预测心血管疾病的严重程度在这个人群.
科学领域:
- 生物化学 生化学
- 遗传学 是一个遗传学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 克洛皮多格雷尔对于预防心血管疾病患者缺血事件至关重要.
- 之前关于克洛皮多格雷尔疗效的研究基本上排除了加勒比海西班牙裔人口.
- 了解不同种族群体对药物反应的变化对于个性化医学至关重要.
研究的目的:
- 调查帕罗酶-1 (PON1) 丰度和活性作为加勒比海西班牙裔克洛皮多格雷尔反应生物标志物的作用.
- 评估PON1作为心血管疾病严重程度的潜在预测因子,在这个研究不足的人群中.
主要方法:
- 招募了36名克洛皮多格雷尔治疗患者 (被分类为反应不佳或正常的患者),11名心血管患者 (阳性对照) 和13名健康志愿者 (负面对照).
- 测量了剩余血小板反应性 (PRU),PON1丰富性 (西部涂抹) 和PON1活性 (酶定量).
- 在512个DNA标本上进行了PON1基因型和哈普洛型分阶段测定,用于loci rs662和rs854560.
主要成果:
- 在研究组之间没有观察到平均相对PON1丰度的显著差异.
- 与两组对照组相比,克洛皮多格雷尔反应较差的患者表现出明显较低的PON1酶活性 (p = 0.004).
- 患有流行PON1单元型的携带者显示PON1活性显著降低,与野生类型相比 (p = 0.005).
结论:
- 在克洛皮多格雷尔耐药的加勒比海西班牙裔患者中,PON1酶活性,而不是丰富性,显著下降.
- 减少PON1活性与克洛皮多格雷尔反应不佳有关,并且可能作为该族群中心血管疾病严重程度的生物标志物.
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