Graduate School of Pharmaceutical Sciences, Kumamoto University.
Headquarters for Admissions and Education, Kumamoto University.
J Atheroscler Thromb. 2024 Sep 1;31(9):1263-1276. doi: 10.5551/jat.64711. Epub 2024 Mar 19.
Paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and protects against atherosclerosis. However, the relationship between functional PON1 Q192R polymorphism, which is associated with the hydrolysis of paraoxon (POXase activity) and atherosclerotic cardiovascular disease (ASCVD), remains controversial. As the effect of PON1 Q192R polymorphism on the HDL function is unclear, we investigated the relationship between this polymorphism and the cholesterol efflux capacity (CEC), one of the biological functions of HDL, in association with the PON1 activity.
The relationship between PON1 Q192R polymorphisms and CEC was investigated retrospectively in 150 subjects without ASCVD (50 with the PON1 Q/Q genotype, 50 with the Q/R genotype, and 50 with the R/R genotype) who participated in a health screening program. The POXase and arylesterase (AREase: hydrolysis of aromatic esters) activities were used as measures of the PON1 activity.
The AREase activity was positively correlated with CEC independent of the HDL cholesterol levels. When stratified by the PON1 Q192R genotype, the POXase activity was also positively correlated with CEC independent of HDL cholesterol. PON1 Q192R R/R genotype carriers had a lower CEC than Q/Q or Q/R genotype carriers, despite having a higher POXase activity. Moreover, in a multiple regression analysis, the PON1 Q192R genotype was associated with the degree of CEC, independent of the HDL cholesterol and POXase activity.
The PON1 Q192R R allele is associated with reduced CEC in Japanese people without ASCVD. Further studies on the impact of this association on the severity of atherosclerosis and ASCVD development are thus called for.
对氧磷酶 1（PON1）与高密度脂蛋白（HDL）结合，可预防动脉粥样硬化。然而，PON1 的功能性 Q192R 多态性与对氧磷（POXase 活性）和动脉粥样硬化性心血管疾病（ASCVD）的水解有关，其与 ASCVD 的关系仍存在争议。由于 PON1 Q192R 多态性对 HDL 功能的影响尚不清楚，因此我们研究了这种多态性与胆固醇流出能力（CEC）之间的关系，CEC 是 HDL 的一种生物学功能，同时还研究了 PON1 活性。
我们对参加健康筛查计划的 150 例无 ASCVD 患者（PON1 Q/Q 基因型 50 例、Q/R 基因型 50 例、R/R 基因型 50 例）进行了回顾性研究，分析了 PON1 Q192R 多态性与 CEC 的关系。我们使用对氧磷酶（POXase：水解对氧磷）和芳基酯酶（AREase：水解芳香酯）活性作为 PON1 活性的指标。
AREase 活性与 CEC 呈正相关，与 HDL 胆固醇水平无关。按 PON1 Q192R 基因型分层时，POXase 活性与 CEC 呈正相关，与 HDL 胆固醇水平无关。与 Q/Q 或 Q/R 基因型携带者相比，PON1 Q192R R/R 基因型携带者的 CEC 较低，但 POXase 活性较高。此外，多元回归分析表明，PON1 Q192R 基因型与 CEC 程度相关，与 HDL 胆固醇和 POXase 活性无关。
在日本无 ASCVD 人群中，PON1 Q192R R 等位基因与 CEC 降低有关。因此，需要进一步研究这种相关性对动脉粥样硬化严重程度和 ASCVD 发展的影响。
