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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1451.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Paraoxonase Status in Coronary Heart Disease

Are Activity and Concentration More Important Than Genotype?

Bharti Mackness; Gershan K. Davies; Wajdi Turkie; Evelyn Lee; David H. Roberts; Elizabeth Hill; Chris Roberts; Paul N. Durrington; Michael I. Mackness

From the University Department of Medicine (B.M., P.N.D., M.I.M.) and the Department of Cardiology (W.T.), Manchester Royal Infirmary, and the Biostatistics Group (E.H., C.R.), School of Epidemiology and Health Sciences, University of Manchester, Manchester, UK, and the Department of Cardiology (G.K.D., E.L., D.H.R.), Royal Victoria Hospital, Blackpool, UK.

Correspondence to Dr Bharti Mackness, University Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL UK. E-mail bmack{at}central.cmht.nwest.nhs.uk

Abstract—— Human serum paraoxonase (PON1) hydrolyzes oxidized lipids in low density lipoprotein (LDL) and could therefore retard the development of atherosclerosis. In keeping with this hypothesis, several case-control studies have shown a relationship between the presence of coronary heart disease (CHD) and polymorphisms at amino acid positions 55 and 192 of PON1, which we associated with a decreased capacity of PON1 to protect LDL against the accumulation of lipid peroxides, but some other studies have not. However, the PON1 polymorphisms are only 1 factor in determining the activity and concentration of the enzyme. Only 3 of the previous 18 studies directly determined PON1 activity and concentration. Therefore, we studied PON1 activity, concentration, and gene distribution in 417 subjects with angiographically proven CHD and in 282 control subjects. We found that PON1 activity and concentration were significantly lower in subjects with CHD than in control subjects (activity to paraoxon 122.8 [3.3 to 802.8] versus 214.6 [26.3 to 620.8] nmol · min^-1 · mL^-1, P<0.001; concentration 71.6 [11.4 to 489.3] versus 89.1 [16.8 to 527.4] µg/mL, P<0.001). There were no differences in the PON1-55 and -192 polymorphisms or clusterin concentration between patients with CHD and control subjects. These results indicate that lower PON1 activity and concentration and, therefore, the reduced ability to prevent LDL lipid peroxidation may be more important in determining the presence of CHD than paraoxonase genetic polymorphisms.

Key Words: paraoxonase • oxidation • coronary heart disease • genetic polymorphisms

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