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The BB-Paraoxonase Genotype Is Associated with Impaired Brachial Reactivity after Acute Hypertriglyceridemia in Healthy Subjects

Department of Geriatric Medicine and Metabolic Diseases, Second University of Naples, I-80138 Naples, Italy; and Department of Experimental Pathology, University of Bologna (M.B., C.F.), I-40100 Bologna, Italy

Address all correspondence and requests for reprints to: Prof. Giuseppe Paolisso, IV Divisione di Medicina Interna e Malattie dell’Invecchiamento, Department of Geriatric Medicine and Metabolic Diseases, Second University of Naples, Piazza Miraglia 2, I-80138 Naples, Italy. E-mail: gpaoliss{at}tin.it

The possible relationship between paraoxonase (PON) gene polymorphism and brachial reactivity in healthy adult subjects in the presence of acute hypertriglyceridemia (HT), as a prooxidant factor, was investigated. In 101 healthy subjects the response to flow- induced vasodilatation was measured before and after Intralipid infusion. In the same subjects the A/B PON polymorphism was detected. The frequency was 0.545 for AA genotype, 0.356 for the AB genotype, and 0.099 for the BB genotype. At baseline all genotype groups had a similar increase in brachial artery diameter and flow. After Intralipid infusion, subjects sharing the BB genotype had a significant decrease vs. baseline values in changes in brachial artery diameter (P for trend < 0.001 vs. the other genotypes), but not in flow. In a subgroup of 55 subjects distributed among the 3 PON genotypes the same study protocol was repeated by buccal nitroglycerine administration to study the endothelium-independent vasodilatation. Again, subjects with the BB genotype had the worse vasodilation (P for trend < 0.001). Furthermore, subjects sharing the BB genotype had the lowest endothelium-independent and -dependent changes in diameter (P for trend < 0.001 vs. the other genotypes) independently of gender ratio, basal plasma triglycerides concentrations, and changes in plasma triglycerides concentrations. In conclusion, our study demonstrates that transient HT decreases vascular reactivity more in subjects with the PON BB genotype than in those with the other PON genotypes.

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