p.Q192R SNP of PON1 seems not to be Associated with Carotid Atherosclerosis Risk Factors in an Asymptomatic and Normolipidemic Brazilian Population Sample

ARQUIVOS BRASILEIROS DE CARDIOLOGIA(2015)

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Abstract
Background: Evidences suggest that paraoxonase 1 (PON1) confers important antioxidant and anti-inflammatory properties when associated with high-density lipoprotein (HDL). Objective: To investigate the relationships between p.Q192R SNP of PON1, biochemical parameters and carotid atherosclerosis in an asymptomatic, normolipidemic Brazilian population sample. Methods: We studied 584 volunteers (females n = 326, males n = 258; 19-75 years of age). Total genomic DNA was extracted and SNP was detected in the TaqMan (R) SNP OpenArray (R) genotyping platform (Applied Biosystems, Foster City, CA). Plasma lipoproteins and apolipoproteins were determined and PON1 activity was measured using paraoxon as a substrate. High-resolution beta-mode ultrasonography was used to measure cIMT and the presence of carotid atherosclerotic plaques in a subgroup of individuals (n = 317). Results: The presence of p.192Q was associated with a significant increase in PON1 activity (RR = 12.30(11.38); RQ = 46.96 (22.35); QQ = 85.35 (24.83) mu mol/min; p < 0.0001), HDL-C (RR= 45 (37); RQ = 62 (39); QQ = 69 (29) mg/ dL; p < 0.001) and apo A-I (RR = 140.76 +/- 36.39; RQ = 147.62 +/- 36.92; QQ = 147.49 +/- 36.65 mg/ dL; p = 0.019). Stepwise regression analysis revealed that heterozygous and p.192Q carriers influenced by 58% PON1 activity towards paraoxon. The univariate linear regression analysis demonstrated that p.Q192R SNP was not associated with mean cIMT; as a result, in the multiple regression analysis, no variables were selected with 5% significance. In logistic regression analysis, the studied parameters were not associated with the presence of carotid plaques. Conclusion: In low-risk individuals, the presence of the p. 192Q variant of PON1 is associated with a beneficial plasma lipid profile but not with carotid atherosclerosis.
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Key words
Paraoxonase-1/genetics,Polymorphism, genetic,Carotid Artery Diseases/physiopathology,Lipoproteins, HDL
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