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Paraoxonase 1 polymorphism Q192R affects the pro-inflammatory cytokine TNF-alpha in healthy males.

ABSTRACT: BACKGROUND: Human paraoxonase 1 (PON1) is an HDL-associated enzyme with anti-oxidant/anti-inflammatory properties that has been suggested to play an important protective role against coronary heart diseases and underlying atherogenesis. The common PON1 Q192R polymorphism (rs662, A>G), a glutamine to arginine substitution at amino acid residue 192, has been analyzed in numerous association studies as a genetic marker for coronary heart diseases, however, with controversial results. FINDINGS: To get a better understanding about the pathophysiological function of PON1, we analyzed the relationships between the Q192R polymorphism, serum paraoxonase activity and serum biomarkers important for atherogenesis. Genotyping a cohort of 49 healthy German males for the Q192R polymorphism revealed an allele distribution of 0.74 and 0.26 for the Q and R allele, respectively, typical for Caucasian populations. Presence of the R192 allele was found to be associated with a significantly increased paraoxonase enzyme activity of 187.8 ± 11.4 U/l in comparison to the QQ192 genotype with 60.5 ± 4.9 U/l. No significant differences among the genotypes were found for blood pressure, asymmetric dimethylarginine, LDL, HDL, triglycerides, and cholesterol. As expected, MIP-2 alpha a cytokine rather not related to atherosclerosis is not affected by the PON1 polymorphism. In contrast to that, the pro-inflammatory cytokine TNF-alpha is enhanced in R192 carriers (163.8 ± 24.7 pg/ml vs 94.7 ± 3.2 pg/ml in QQ192 carriers). CONCLUSIONS: Our findings support the hypothesis that the common PON1 R192 allele may be a genetic risk factor for atherogenesis by inducing chronic low-grade inflammation.

SUBMITTER: Luersen K

PROVIDER: S-EPMC3101657 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Paraoxonase 1 polymorphism Q192R affects the pro-inflammatory cytokine TNF-alpha in healthy males.

Lüersen Kai K Schmelzer Constance C Boesch-Saadatmandi Christine C Kohl Christine C Rimbach Gerald G Döring Frank F

BMC research notes 20110510

<h4>Background</h4>Human paraoxonase 1 (PON1) is an HDL-associated enzyme with anti-oxidant/anti-inflammatory properties that has been suggested to play an important protective role against coronary heart diseases and underlying atherogenesis. The common PON1 Q192R polymorphism (rs662, A>G), a glutamine to arginine substitution at amino acid residue 192, has been analyzed in numerous association studies as a genetic marker for coronary heart diseases, however, with controversial results.<h4>Find ...[more]

PMID: 21569287

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Project description:IntroductionThe present study aimed to investigate the association of the paraoxonase 1 (PON1) Q192R polymorphism with coronary artery disease (CAD) and cardiometabolic risk factors in Iranian patients suspected of CAD.MethodsThis cross-sectional study was conducted on 428 patients undergoing angiography. The data related to demographic information and physical activity were collected by valid and reliable questionnaires. The PON-1 genotypes were detected by the polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) technique. The Gensini and SYNTAX score, anthropometric measurements, and biochemical and clinical parameters were measured by standard protocols.Results and discussionFindings indicated that the odds of obesity was significantly higher in people with the RR genotype compared to the QQ genotype carriers (OR: 2.95 CI: 1.25-6.93, P = 0.014) and also odds of low high-density lipoprotein cholesterol (HDL-C) was marginally higher (OR: 2.31 CI: 0.97-5.49, P = 0.056). There was no significant association between other CAD risk factors with PON1 Q192R polymorphism (P > 0.05). Further analysis showed a significant interaction between sex and 192QR (P = 0.019) and 192 RR (P = 0.007) genotypes on body mass index (BMI). More specifically, the risk of obesity in men carrying the RR genotype was 3.38 times (OR: 3.38 CI: 1.08-10.58, P = 0.036). Also, a significant joint effect of the RR genotype and sex on HDL-C was seen (P = 0.003). The stratification based on sex showed that the risk of low HDL-C is significantly higher in women carrying the RR genotype (OR: 6.18 CI: 1.21-31.46, P = 0.028). A marginal sex-genotype interaction was also found in the risk of elevated alanine aminotransferase (ALT) (P = 0.057). In summary, the findings showed that the risk of obesity and low HDL-C was higher in people carrying the RR genotype. On the other hand, a Q192R polymorphism-sex interaction was observed on the risk of obesity, elevated ALT, and low HDL-C.

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Paraoxonase 1 polymorphism Q192R affects the pro-inflammatory cytokine TNF-alpha in healthy males.

Publications

Paraoxonase 1 polymorphism Q192R affects the pro-inflammatory cytokine TNF-alpha in healthy males.

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