Arylesterase activity of paraoxonase 1 (PON1) on HDL3 and HDL2: Relationship with Q192R, C-108T, and L55M polymorphisms

Abstract

Background Controversy exists regarding the role of the subfractions of high-density lipoproteins (HDL 2 and HDL 3 ) in cardiovascular disease. The functionality of these particles, and their protective role, is due in part to the paraoxonase 1 (PON1) presence in them. The polymorphisms rs662 (Q192R, A/G), rs854560 (L55 M, T/A), and rs705379 (C-108T) of the PON1 gene have been related to enzyme activity and, with the anti-oxidative capacity of the HDL. The objective was to determine the arylesterase PON1 activity in HDL 3 and HDL 2 and its relationship with the polymorphisms mentioned, in a young population. Methods The polymorphisms were determined through mini-sequencing (SnaPshot). The HDL subpopulations were separated via ionic precipitation, cholesterol was measured with enzymatic methods, and PON1 activity was measured through spectrophotometry. Results The results show that the PON1 polymorphisms do not influence the cholesterol in the HDL. A variation between 40.02 and 43.9 mg/dL was in all the polymorphisms without significant differences. Additionally, PON1 activity in the HDL 3 subfractions was greater (62.83 ± 20 kU/L) than with HDL 2 (35.8 ± 20.8 kU/L) in the whole population and in all the polymorphisms (p < 0.001), and it was independent of the polymorphism and differential arylesterase activity in the Q192R polymorphism (QQ > QR > RR). Thus, 115.90 ± 30.7, 88.78 ± 21.3, 65.29 ± 10.2, respectively, for total HDL, with identical behavior for HDL 3 and HDL 2 . Conclusions PON1 polymorphisms do not influence the HDL -c , and the PON activity is greater in the HDL 3 than in the HDL 2 , independent of the polymorphism, but it is necessary to delve into the functionality of these findings in different populations.

PON1, APOE and SDF-1 Gene Polymorphisms and Risk of Retinal Vein Occlusion: A Case-Control Study

“…On the other hand, L55M is regarded to influence the PON1 concentrations but not the enzymatic activity directly. The L55 allozyme is associated with increased serum PON1 concentrations compared to the 55M due to its greater stability and resistance to proteolysis [ 58 , 59 , 60 ].…”

Alelos -108C/T, L55M y Q192R de paraoxoasa 1 (pon 1) en población del eje cafetero de Colombia

“…PON1 may protect against cardiovascular disease (CVD. Un estudio en Colombia relacionó los resultados genotípicos con la medida de la actividad de pon 1, confirmando que el polimorfismo Q192 R determina en parte la actividad de la pon 1 y que su efecto es mediado por el alelo Q, ya que este alelo parece tener mayor actividad que el R [21].…”