PON1Q192R基因多态性对急性冠脉综合征患者他汀治疗后血脂早期达标的影响

急性冠脉综合征（ACS）患者需使用他汀调脂、抗炎、抗氧化及预防不良事件。临床中他汀治疗后血脂达标率不容乐观。人源性对氧磷酶-1（paraoxonase-1, PON1）是一种高密度脂蛋白胆固醇相关的酯酶，具有抗动脉粥样硬化及保护心血管作用。PON1Q192R基因多态性决定了PON1酶抑制低密度脂蛋白胆固醇氧化修饰的酶活性。前期研究中我们发现其RR基因型是ACS患者经皮冠状动脉介入治疗（PCI）术后再次植入支架事件的独立危险因素。我们推测PON1Q192R基因多态性可能影响ACS患者他汀治疗反应性，从而可预测并识别高危风险患者。本项目拟通过前瞻性队列研究，收集ACS患者基线及强化他汀治疗1月后血脂谱，检测PON1Q192R基因型，评价其基因多态性对他汀治疗后血脂早期达标的影响，探讨他汀治疗后血脂早期达标的预测因素。研究将有助于明确PON1Q192R的风险基因型，为后续个体化治疗提供指导意义。

Patients with acute coronary syndrome (ACS) should be treated with statins for lipid regulation, anti-inflammation, antioxidation and prevention of adverse events. In clinical practice the number of patients achieving serum lipid goals is low. Human paraoxonase-1 (PON1) is a high density lipoprotein cholesterol associated esterase, which has anti-atherosclerosis and cardiovascular protective effects. Polymorphism of PON1Q192R gene determines the activity of PON1 enzyme in inhibiting the oxidative modification of low density lipoprotein cholesterol. In previous study we found that the RR genotype was an independent risk factor for re-stenting in ACS patients after percutaneous coronary intervention (PCI). We hypothesize that PON1Q192R gene polymorphism may affect the response to statin treatment in ACS patients, so it can be used to predict and identify high-risk patients. In patients with ACS, a prospective cohort study will be conducted to collect lipid profiles at baseline and after 1 month of intensive statin treatment, to detect the PON1 Q192R genotype, to evaluate the effect of gene polymorphism on achieving serum lipid goals early after statin treatment, and to investigate the predictors of achieving serum lipid goals early after statin treatment. The study will be helpful to identify the risky genotype of PON1 Q192R and provide guidance for subsequent individualized treatment.