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Atherosclerosis. 2003 Mar;167(1):141-8.

A paraoxonase gene polymorphism, PON 1 (55), as an independent risk factor for increased carotid intima-media thickness in middle-aged women.

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Dipartimento di Biochimica e Biotecnologie Mediche, Università Federico II di Napoli and CEINGE scarl, via S. Pansini 5, Italy.


Paraoxonase (PON) gene polymorphisms have been proposed as genetic markers of risk for cardiovascular disease (CVD). Sporadic results suggest they are correlated with intima-media thickness (IMT), an indicator of preclinical atherosclerotic disease. We have investigated whether polymorphisms PON 1 (M/L) 55, (Q/R) 192, PON 2 (S/C) 311 are related to site-specific carotid plaques in 310 middle-aged women. Subjects were also investigated for physical and biochemical parameters including oxidative markers to evaluate their effect on development of atherosclerotic plaques (IMT>1.2 mm) identified by high resolution B-mode ultrasound. We demonstrate that PON 1 (LL+ML) 55 is associated with plaques both at the bifurcation (OR=2.40; 95% CI 1.00-5.90) and at the common carotid artery (OR=2.75; 95% CI 1.01-7.50), and to the total number of plaques at any site (P<0.05). This polymorphism is an independent parameter with respect to other variables that are significantly associated with plaques, i.e. systolic blood pressure (OR=2.06; 95% CI 1.11-3.81) and oxidized low-density lipoprotein (LDL) antibodies (OR=1.96; 95% CI 1.05-3.69) in cases of common carotid plaques, and lipid peroxides (OR=1.86; 95% CI 1.00-3.50) in cases of bifurcation plaques. In conclusion, PON 1 (LL+ML) 55 but not PON 1 (Q/R) 192 or PON 2 (S/C) 311, appears to be an independent risk factor for increased carotid IMT in middle-aged women.

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