The Association of the Cholesterol Efflux Capacity with the Paraoxonase 1 Q192R Genotype and the Paraoxonase Activity.

Autor:	Oniki K; Graduate School of Pharmaceutical Sciences, Kumamoto University., Ohura K; Graduate School of Pharmaceutical Sciences, Kumamoto University.; Headquarters for Admissions and Education, Kumamoto University., Endo M; Graduate School of Pharmaceutical Sciences, Kumamoto University., Akatwijuka D; Graduate School of Pharmaceutical Sciences, Kumamoto University., Matsumoto E; Graduate School of Pharmaceutical Sciences, Kumamoto University., Nakamura T; Graduate School of Pharmaceutical Sciences, Kumamoto University., Ogata Y; Japanese Red Cross Kumamoto Health Care Center., Yoshida M; Japanese Red Cross Kumamoto Health Care Center., Harada-Shiba M; Cardiovascular Center, Osaka Medical and Pharmaceutical University.; Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute., Saruwatari J; Graduate School of Pharmaceutical Sciences, Kumamoto University., Ogura M; Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute.; Department of Clinical Laboratory Technology, Faculty of Medical Science, Juntendo University., Imai T; Graduate School of Pharmaceutical Sciences, Kumamoto University.; Daiichi University of Pharmacy.
Jazyk:	angličtina
Zdroj:	Journal of atherosclerosis and thrombosis [J Atheroscler Thromb] 2024 Sep 01; Vol. 31 (9), pp. 1263-1276. Date of Electronic Publication: 2024 Mar 19.
DOI:	10.5551/jat.64711
Abstrakt:	Aims: 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. Methods: 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. Results: 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. Conclusions: 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.
Databáze:	MEDLINE
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