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Nutrition and Disease

Arylesterase Activity and Antioxidant Status Depend on PON1-Q192R and PON1-L55M Polymorphisms in Subjects with Increased Risk of Cardiovascular Disease Consuming Walnut-Enriched Meat^1,2

³ Departamento de Nutrición y Bromatología I (Nutrición), ⁴ Biotransformations Group, Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid E-28040, Spain; and ⁵ Departamento de Medicina Preventiva y CIBER Fisiopatología de la Obesidad y Nutrición, Facultad de Medicina, Universidad de Valencia, Valencia E-46010, Spain

^* To whom correspondence should be addressed. E-mail: frasan{at}farm.ucm.es.

Human paraoxonase (PON1) exists in 2 major polymorphic forms and has been shown to protect LDL and HDL against oxidation. The aim of this study was to assess the differences between subjects at increased risk of cardiovascular disease (CVD), taking into account the effects of PON1-Q192R and PON1-L55M polymorphisms on 1) basal serum arylesterase activity, lipid peroxidation (LPO), and LDL-cholesterol (LDL-C), HDL-C, total cholesterol (TC), and oxidized-LDL (ox-LDL) concentrations; 2) the relations between arylesterase activity and lipid variables; and 3) the effect of walnut-enriched meat (WM) consumption on arylesterase activity and lipid variables. Twenty-three Caucasians at increased risk of CVD were randomly assigned to diet order groups in a crossover, nonblinded, placebo-controlled trial, consisting of two 5-wk experimental periods [WM and control meat (CM)]. Significant PON1-L55M x PON1-Q192R interactions affected basal serum HDL-C (P = 0.019), LDL-C (P = 0.028) and TC (P = 0.022) and tended to affect arylesterase activity (P = 0.083). Basal arylesterase activity was positively correlated with basal HDL-C (r = 0.53; P < 0.05) and TC (r = 0.43; P < 0.05) and negatively correlated with LPO (r = –0.70; P < 0.01) and the ox-LDL:LDL ratio (r = –0.63; P < 0.01). WM decreased arylesterase activity in PON1-55M carriers (P = 0.012) but not in PON1-L55 individuals, and decreased LPO concentrations in PON1-192R carriers (P = 0.031) but not in PON1-Q192 subjects. To conclude, serum TC, HDL-C, and LDL-C concentrations and arylesterase activity depend on the interaction of PON1-L55M and PON1-Q192R polymorphisms. However, the PON1-Q192R polymorphism is more closely related to antioxidant status. Both polymorphisms modulate the effect of WM consumption on CVD biomarkers.