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

Lüersen K, Schmelzer C, Boesch-Saadatmandi C, Kohl C, Rimbach G, Döring F - BMC Res Notes (2011)

Bottom Line: 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.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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Human Nutrition and Food Science, Molecular Prevention, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, 24118 Kiel, Germany. sek@molprev.uni-kiel.de.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of the PON1 Q192R polymorphism on inflammatory biomarkers. (A) TNF-alpha, (B) MCP-1 and (C) MIP-2-alpha levels were determined in the sera of Q/Q (n = 25) and Q/R+R/R (n = 24) male subjects. Data represent means ± SEM (** p ≤ 0.01).
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Figure 2: Effect of the PON1 Q192R polymorphism on inflammatory biomarkers. (A) TNF-alpha, (B) MCP-1 and (C) MIP-2-alpha levels were determined in the sera of Q/Q (n = 25) and Q/R+R/R (n = 24) male subjects. Data represent means ± SEM (** p ≤ 0.01).

Mentions: Finally, we analyzed the effect of the Q192R polymorphism on the inflammatory biomarkers TNF-alpha, MCP-1 and MIP-2-alpha. As shown in Figure 2A, the mean level of TNF-alpha for the Q/Q group was found to be 94.7 ± 3.2 pg/ml. In the sera of Q/R and R/R individuals the respective level was significantly enhanced with a mean value of 163.8 ± 24.7 pg/ml (p = 0.007; unpaired two-sided Student's t-test). Furthermore, the inflammatory biomarker MCP-1 was slightly but not significantly enhanced in Q/R and R/R individuals when compared with the Q/Q group (202.0 ± 30.7 versus 173.0 ± 11.2 ng/ml) (Figure 2B). In contrast to that, MIP-2-alpha levels were not affected by the Q192R polymorphism (258.2 ± 13.7 versus 248.1 ± 12.9 pg/ml; Figure 2C).


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

Lüersen K, Schmelzer C, Boesch-Saadatmandi C, Kohl C, Rimbach G, Döring F - BMC Res Notes (2011)

Effect of the PON1 Q192R polymorphism on inflammatory biomarkers. (A) TNF-alpha, (B) MCP-1 and (C) MIP-2-alpha levels were determined in the sera of Q/Q (n = 25) and Q/R+R/R (n = 24) male subjects. Data represent means ± SEM (** p ≤ 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3101657&req=5

Figure 2: Effect of the PON1 Q192R polymorphism on inflammatory biomarkers. (A) TNF-alpha, (B) MCP-1 and (C) MIP-2-alpha levels were determined in the sera of Q/Q (n = 25) and Q/R+R/R (n = 24) male subjects. Data represent means ± SEM (** p ≤ 0.01).
Mentions: Finally, we analyzed the effect of the Q192R polymorphism on the inflammatory biomarkers TNF-alpha, MCP-1 and MIP-2-alpha. As shown in Figure 2A, the mean level of TNF-alpha for the Q/Q group was found to be 94.7 ± 3.2 pg/ml. In the sera of Q/R and R/R individuals the respective level was significantly enhanced with a mean value of 163.8 ± 24.7 pg/ml (p = 0.007; unpaired two-sided Student's t-test). Furthermore, the inflammatory biomarker MCP-1 was slightly but not significantly enhanced in Q/R and R/R individuals when compared with the Q/Q group (202.0 ± 30.7 versus 173.0 ± 11.2 ng/ml) (Figure 2B). In contrast to that, MIP-2-alpha levels were not affected by the Q192R polymorphism (258.2 ± 13.7 versus 248.1 ± 12.9 pg/ml; Figure 2C).

Bottom Line: 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.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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Human Nutrition and Food Science, Molecular Prevention, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, 24118 Kiel, Germany. sek@molprev.uni-kiel.de.

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.

No MeSH data available.


Related in: MedlinePlus