Q192R PARAOXONASE(PON)1 POLYMORPHISM, INSULIN SENSITIVITY AND ENDOTHELIAL FUNCTION IN ESSENTIAL HYPERTENSIVE MEN

AIMS: Essential hypertension is characterized by increased reactive oxygen species generation harmful for insulin sensitivity and nitric oxide (NO)-mediated vasomotor function, a noxious effect that paraoxoase(PON)1, an antioxidant circulating HDL-bound esterase, may counteract. The PON1 gene contains several polymorphisms including a glutamine (Q) to arginine (R) transition at position 192 encoding circulating allozymes with higher antioxidant activity that might influence both parameters. METHODS: Q192R was determined by polymerase chain reaction in 72 never treated, glucose-tolerant, uncomplicated essential hypertensive men. Insulin sensitivity was assessed by HOMA and endothelial function by forearm vasodilation (strain-gauge venous plethysmography) to intra-arterial acetylcholine with sodium nitroprusside as a NO–independent control. Additional evaluation variables included 24-hr BP, lipids, BMI, smoking status and Metabolic Syndrome (MetS) by ATP-III criteria. R192 was considered the rare allele and its associations analyzed by dominant models (Q/Q vs Q/R+R/R). RESULTS: Genotype frequencies were consistent with the Hardy-Weinberg equilibrium. HOMA was lower and insulin resistance (the upper fourth of HOMA values distribution) less prevalent in Q/R+R/R carriers in whom ACH-mediated vasodilatation was greater and endothelial dysfunction (the bottom fourth of ACHAUC values distribution) less frequent than in Q/Q homozygotes. Q192R polymorphism and MetS were unrelated parameters despite their strong association with insulin resistance. 24-hr BP, BMI, lipids, smoking habits were homogeneously distributed across genotypes. CONCLUSIONS: Q192R polymorphism associates differentially with insulin sensitivity and endothelial function in essential hypertensive men.