Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score.
OBJECTIVE
Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more.


METHODS
Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates.


RESULTS
Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol.


CONCLUSIONS
Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity.
Programa de Pós-Graduação em Ciências da Saúde, Universidade Estadual de Londrina (UEL), Londrina, PR, Brasil.
Andre de
A
Souza-Nogueira
Departamento de Patologia, Análises Clínicas e Toxicológicas, UEL, Londrina, PR, Brasil.
Alissana Ester
AE
Camargo
Secretaria de Saúde do Estado do Paraná, Londrina, PR, Brasil.|Programa de Pós-Graduação em Saúde Pública, UEL, Londrina, PR, Brasil.
Felipe Assan
FA
Remondi
Departamento de Patologia, Análises Clínicas e Toxicológicas, UEL, Londrina, PR, Brasil.|Programa de Pós-Graduação em Saúde Pública, UEL, Londrina, PR, Brasil.
Monica Maria Bastos
MM
Paoliello
Departamento de Ciências do Genoma e Medicina, Divisão de Genética Médica, Universidade de Washington, Seattle, Washington, EUA.
Rebecca J
RJ
Richter
Departamento de Ciências do Genoma e Medicina, Divisão de Genética Médica, Universidade de Washington, Seattle, Washington, EUA.
Clement E
CE
Furlong
Programa de Pós-Graduação em Ciências da Saúde, Universidade Estadual de Londrina (UEL), Londrina, PR, Brasil.|Departamento de Patologia, Análises Clínicas e Toxicológicas, UEL, Londrina, PR, Brasil.
Decio Sabbatini
DS
Barbosa
Centro de Pesquisa de Impacto Estratégico, Faculdade de Medicina, Universidade de Deakin, Geelong, Victoria, Austrália.
Michael
M
Maes
Programa de Pós-Graduação em Ciências da Saúde, Universidade Estadual de Londrina (UEL), Londrina, PR, Brasil.|Departamento de Ciências Fisiológicas, UEL, Londrina, PR, Brasil.
Estefania Gastaldello
EG
Moreira
D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D006868:Hydrolysis; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012016:Reference Values; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D043303:Aryldialkylphosphatase