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Unexpectedly higher diazoxon hydrolysis by serum paraoxonase-1 in coronary heart disease
Bharti Mackness1, Mike Mackness1
1Avda. Princip D'Espanya, 43892 Miami Playa, Tarragona, Spain.
Insights
Serum paraoxonase-1 (PON1) activity toward diazoxon was significantly higher in individuals with coronary heart disease (CHD). This finding suggests potential diagnostic and mechanistic implications for PON1 in CHD, pending further research.
Area of Science:
- Biochemistry
- Cardiovascular Medicine
- Genetics
Background:
- Low serum paraoxonase-1 (PON1) activity is linked to coronary heart disease (CHD).
- PON1 plays a role in hydrolyzing various substrates, but its specific role in CHD is not fully understood.
- Investigating PON1 activity with specific substrates like diazoxon is crucial for understanding its association with CHD.
Purpose of the Study:
- To investigate the rate of diazoxon hydrolysis by PON1 in a population with CHD.
- To compare PON1 activity and genotypes between CHD patients and controls.
- To explore the relationship between PON1 polymorphisms (PON1-55 and PON1-192) and diazoxon hydrolysis in CHD.
Main Methods:
- A case-control study involving 410 subjects with CHD and 274 controls.
- Measurement of PON1 activity using paraoxon and diazoxon substrates.
- Determination of serum PON1 concentration and genotyping for PON1-55 and PON1-192 polymorphisms.
Main Results:
- No significant differences in PON1-55 or PON1-192 genotype distribution between CHD patients and controls.
- PON1 activity towards diazoxon (DIAZ) was significantly higher (+160%) in the CHD group compared to controls.
- DIAZ activity showed significant differences across PON1-192 and PON1-55 genotypes in both populations, with specific orders observed for QQ > QR > RR and LL > LM > MM, respectively.
Conclusions:
- The significantly higher diazoxon hydrolysis rate in CHD patients warrants further investigation.
- Replication of these findings with other PON1 substrates and in diverse populations is essential.
- These results may have significant diagnostic and mechanistic implications for understanding the role of PON1 in CHD.
Objectives:
Low serum PON1 activities (paraoxon, phenyl-acetate or lactone substrates) are associated with coronary heart disease (CHD). We investigated the rate of diazoxon hydrolysis by PON1 in a population with CHD.
Design & Methods:
Case- control study of 410 subjects with CHD and 274 controls. PON1 activity towards paraoxon and diazoxon, PON1 serum concentration and the PON1-55 and 192 polymorphisms were determined.
Results:
There were no differences in the distribution of the PON1-55 or PON1-192 genotypes between the CHD and controls, however, PON1 activity towards diazoxon (DIAZ) was significantly (+160%) higher in CHD. In the control population, DIAZ was significantly different between the PON1-192 genotypes in the order QQ > QR > RR (P < .001). However, in CHD the order was QQ > QR = RR. In CHD DIAZ was significantly higher in all the PON1-192 and 55 genotypes compared to controls. In both populations DIAZ was significantly different between the PON1-55 genotypes in the order LL > LM > MM (P < .001).
Conclusion:
If this result can be replicated in other studies and/or with other PON1 substrates, there may be major diagnostic and mechanistic implications for the relationship of PON1 and CHD.
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