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Paraoxonase 1 status in the Thai population
Wimon Phuntuwate1, Chuthamanee Suthisisang2, Banhan Koanantakul3
1Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Sri Ayudhaya Road, 10400, Bangkok, Thailand.
Journal of Human Genetics
|June 1, 2005
Summary
Human serum paraoxonase 1 (PON1) gene polymorphisms significantly impact enzyme activity, influencing protection against atherosclerosis. These genetic variations affect PON1 activity differently depending on the substrate, with implications for HDL cholesterol levels.
Area of Science:
- Biochemistry
- Genetics
- Cardiovascular Disease Research
Background:
- Human serum paraoxonase 1 (PON1) is an HDL-associated enzyme that prevents LDL and HDL oxidation, offering protection against atherosclerosis.
- Genetic variations within the PON1 gene, specifically polymorphisms, are known to influence its activity and, consequently, its protective role.
Purpose of the Study:
- To identify four polymorphisms in the human PON1 gene (L55M, Q192R, T-108C, G-909C) in healthy Thai individuals.
- To investigate the influence of these identified PON1 polymorphisms on serum PON1 enzyme activity towards paraoxon, phenylacetate, and diazoxon.
- To examine the relationship between PON1 polymorphisms, serum PON1 activity, and concentrations of HDL cholesterol and apo AI.
Main Methods:
- Genotyping of 202 healthy Thai individuals for four PON1 gene polymorphisms (L55M, Q192R, T-108C, G-909C).
- Measurement of serum PON1 enzyme activity using paraoxon, phenylacetate, and diazoxon as substrates.
- Statistical analysis to determine the association between genotypes, enzyme activity, and serum lipid parameters, including HDL cholesterol and apo AI.
- Assessment of linkage disequilibrium among the polymorphic sites.
Main Results:
- PON1 L55M, Q192R, and G-909C polymorphisms significantly affected serum PON1 activity towards paraoxon, with specific genotype-phenotype correlations observed (e.g., 55LL > 55LM/55MM).
- PON1 Q192R and G-909C polymorphisms influenced diazoxon activity in the opposite direction to paraoxon activity.
- PON1 L55M polymorphism was associated with phenylacetate activity variation, while T-108C had no significant effect on any substrate.
- Linkage disequilibrium was found among Q192R, L55M, T-108C, and G-909C polymorphisms.
- Serum PON1 activity for paraoxon and phenylacetate correlated positively with HDL cholesterol and apo AI, but not diazoxon activity.
Conclusions:
- PON1 polymorphisms significantly influence serum PON1 activity, with the impact being substrate-dependent.
- The identified PON1 polymorphisms are associated with variations in enzyme activity, potentially affecting the enzyme's role in preventing atherosclerosis.
- The findings highlight the physiological relevance of PON1 genetic variations in modulating enzyme function and its relationship with cardiovascular risk factors like HDL-C.