Paraoxonase 1 activity, concentration and genotype in cardiovascular disease.
OBJECTIVE
To provide up-to-date information on the most recent advances in the epidemiology, biochemistry and molecular biology of the antiatherosclerotic enzyme paraoxonase 1.


RESULTS
Case-control and prospective studies published during the period covered by this review have indicated that paraoxonase 1 'status' (i.e. activity and/or concentration) was a more important coronary heart disease risk factor than the paraoxonase 1 genetic polymorphisms. New findings on the role of paraoxonase 1 in homocysteine metabolism are reviewed, as are advances in the nutritional and pharmacological regulation of paraoxonase 1. The recent controversy over whether paraoxonase 1 or platelet-activating factor acetylhydrolase is responsible for the antioxidant activity of high-density lipoprotein is also addressed.


CONCLUSIONS
In the light of recent findings, we believe that genetic epidemiological studies of the paraoxonase 1 polymorphisms in relation to coronary heart disease should no longer be undertaken unless they are very large and prospective in nature. More research should be undertaken to discover the biochemical mechanisms underlying the mode of action of paraoxonase 1 and the factors which modulate its activity and/or concentration.


BACKGROUND
Bharti Mackness is funded by the International HDL Research Awards Programme. All authors receive research funding from the British Heart Foundation and Diabetes UK.
Mackness
Mike
M
University Department of Medicine, Manchester Royal Infirmary, Manchester, UK. mike.mackness@cnmc.nhs.uk
Durrington
Paul
P
Mackness
Bharti
B
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics; D000975:Antioxidants / Q000378:metabolism; D001161:Arteriosclerosis / Q000201:enzymology / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000201:enzymology* / Q000235:genetics*; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008954:Models, Biological; D011110:Polymorphism, Genetic
D000975:Antioxidants; D008075:Lipoproteins, HDL; D006710:Homocysteine; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase