title: The influence of PON1 192 polymorphism on endothelial function in diabetic subjects with or without hypertension.
abstract: Hypertension and type 2 diabetes mellitus (T2DM) cause endothelial dysfunction probably through increased oxidant stress. Paraoxonase (PON1) is an high-density lipoprotein (HDL)-linked anti-oxidant enzyme whose capacity is influenced by a genetic polymorphism at codon 192. In the present study we have investigated the role of PON1 polymorphism on endothelial function in subjects with T2DM with or without hypertension. Three groups of male subjects were enrolled: 65 healthy control subjects without T2DM or hypertension (CON), 51 with only T2DM (DM), and 67 with both hypertension and T2DM (HYP+DM). The PON1 Gln192Arg polymorphism was determined by polymerase chain reaction (PCR) amplification and restriction analysis. Endothelial function was evaluated as flow-mediated vasodilatation (FMD) of the brachial artery after forearm ischemia. Data were analyzed according to the presence or absence of the Arg allele. Subjects with T2DM had markedly impaired FMD, compared with those of the CON group. In the CON and HYP+DM groups no difference was observed in FMD between subjects homozygous for the Gln allele and those carrying the Arg allele. In the DM group FMD was lower among those carrying the Arg allele compared with Gln/Gln homozygotes (2.1+/-2.4% vs. 6.2+/-5.2%, p=0.002). In conclusion, the present findings demonstrated that FMD was less impaired in normotensive diabetic subjects homozygous for the Gln allele, consistent with the notion that this isoform has a more effective antioxidant action that serves to protect circulating low-density lipoprotein (LDL). Hypertension seems to abolish the protective effect of the Gln isoform. These findings, however, warrant further investigation to clarify their clinical import.
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica G. Salvatore, Magna Graecia University, Catanzaro, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Irace
authors.forename: Claudio
authors.initials: C
authors.lastname: Cortese
authors.forename: Elio
authors.initials: E
authors.lastname: Fiaschi
authors.forename: Faustina
authors.initials: F
authors.lastname: Scavelli
authors.forename: Laura
authors.initials: L
authors.lastname: Liberatoscioli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Federici
authors.forename: Agostino
authors.initials: A
authors.lastname: Gnasso
mesh_terms: D000483:Alleles; D043303:Aryldialkylphosphatase / Q000235:genetics*; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000503:physiopathology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014664:Vasodilation / Q000235:genetics / Q000502:physiology
chemical_list: D043303:Aryldialkylphosphatase; C468406:PON1 protein, human