title: Q192R Paraoxonase (PON)1 Polymorphism, Insulin Sensitivity, and Endothelial Function in Essential Hypertensive Men.
abstract: OBJECTIVE
  Essential hypertension is characterized by increased reactive oxygen species (ROS) generation harmful for insulin sensitivity and nitric oxide (NO)-mediated vasomotor function, a noxious effect that paraoxonase (PON)1, an antioxidant circulating high-density lipoprotein (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 homeostasis model assessment (HOMA) and endothelial function by forearm vasodilation (strain-gage venous plethysmography) to intra-arterial acetylcholine (ACH) with sodium nitroprusside (NIP) as a NO-independent control. Additional evaluation variables included 24-hour blood pressure (BP), lipids, BMI, smoking status, and metabolic syndrome (MetS) by Adult Treatment Panel (ATP)-III criteria. R192 was considered as 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 ACH(AUC) values distribution) less frequent than in Q/Q homozygotes. Q192R polymorphism and MetS were unrelated parameters despite their common association with insulin resistance. 24-hour BP, BMI, lipids, and smoking habits were homogeneously distributed across genotypes.
  
  
  CONCLUSIONS
  Q192R polymorphism associates differentially with insulin sensitivity and endothelial function in essential hypertensive men.
authors.affiliation: Dipartimenti di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica, Università di Pisa, Pisa, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Dell'Omo
authors.affiliation: Medicina Clinica e Sperimentale, Università di Pisa, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Penno
authors.affiliation: Istituto di Biologia e Biotecnologia Agraria, CNR, Pisa, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pucci
authors.affiliation: Medicina Clinica e Sperimentale, Università di Pisa, Pisa, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lucchesi
authors.affiliation: Medicina Clinica e Sperimentale, Università di Pisa, Pisa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Del Prato
authors.affiliation: Dipartimenti di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica, Università di Pisa, Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pedrinelli
keywords: Q192R polymorphism; endothelial dysfunction; essential hypertension; insulin resistance; paraoxonase-1
references.citation: Nat Genet. 1993 Jan;3(1):73-6
references.pmid: 8098250
references.citation: Adv Cyclic Nucleotide Res. 1978;9:131-43
references.pmid: 27075
references.citation: Hypertens Res. 2008 Mar;31(3):507-13
references.pmid: 18497471
references.citation: J Mol Med (Berl). 2003 Dec;81(12):766-79
references.pmid: 14551701
references.citation: J Hypertens. 2006 May;24(5):931-7
references.pmid: 16612256
references.citation: Nephrol Dial Transplant. 2009 Jun;24(6):1864-9
references.pmid: 19176688
references.citation: N Engl J Med. 1987 Aug 6;317(6):350-7
references.pmid: 3299096
references.citation: JAMA. 2001 May 16;285(19):2486-97
references.pmid: 11368702
references.citation: Free Radic Biol Med. 2005 Jan 15;38(2):153-63
references.pmid: 15607899
references.citation: Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2803-12
references.pmid: 22982463
references.citation: Nucleic Acids Res. 1976 Sep;3(9):2303-8
references.pmid: 987581
references.citation: Diabetes Care. 2000 Jan;23(1):57-63
references.pmid: 10857969
references.citation: J Clin Endocrinol Metab. 2001 Mar;86(3):1078-82
references.pmid: 11238489
references.citation: Circulation. 2000 Feb 22;101(7):740-3
references.pmid: 10683346
references.citation: Curr Pharm Des. 2013;19(15):2737-46
references.pmid: 23092327
references.citation: Physiol Res. 2005;54(3):287-93
references.pmid: 15974833
references.citation: Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4108-13
references.pmid: 8633024
references.citation: Metabolism. 2001 Jul;50(7):805-11
references.pmid: 11436186
references.citation: J Clin Endocrinol Metab. 2001 Nov;86(11):5457-64
references.pmid: 11701722
references.citation: Circulation. 2006 Apr 18;113(15):1888-904
references.pmid: 16618833
references.citation: Handb Exp Pharmacol. 2006;(176 Pt 2):249-83
references.pmid: 16999229
references.citation: Exp Diabetes Res. 2012;2012:231502
references.pmid: 21960992
references.citation: J Atheroscler Thromb. 2003;10(2):85-92
references.pmid: 12740482
references.citation: N Engl J Med. 1990 Jul 5;323(1):22-7
references.pmid: 2355955
references.citation: Am J Physiol Heart Circ Physiol. 2000 Jan;278(1):H175-83
references.pmid: 10644597
references.citation: Diabetes Res Clin Pract. 2003 May;60(2):79-85
references.pmid: 12706315
references.citation: Atherosclerosis. 2004 Feb;172(2):383-9
references.pmid: 15019550
references.citation: FEBS Lett. 1998 Feb 13;423(1):57-60
references.pmid: 9506841
references.citation: J Am Coll Cardiol. 2003 Mar 19;41(6):938-45
references.pmid: 12651037
references.citation: Atherosclerosis. 2004 Jul;175(1):23-30
references.pmid: 15186943
references.citation: Front Immunol. 2013 Aug 19;4:237
references.pmid: 23966996
references.citation: Metabolism. 2003 Feb;52(2):146-51
references.pmid: 12601623
references.citation: J Hypertens. 2007 Jul;25(7):1389-95
references.pmid: 17563560
references.citation: Proc Nutr Soc. 2004 Feb;63(1):153-60
references.pmid: 15070445
references.citation: Nature. 1980 Nov 27;288(5789):373-6
references.pmid: 6253831
references.citation: J Hum Hypertens. 2009 May;23(5):332-8
references.pmid: 19078990
references.citation: Mayo Clin Proc. 2008 Feb;83(2):158-64
references.pmid: 18241625
references.citation: Am J Physiol Endocrinol Metab. 2008 Jan;294(1):E15-26
references.pmid: 17957034
references.citation: Free Radic Biol Med. 2011 Sep 1;51(5):993-9
references.pmid: 21163347
references.citation: Curr Hypertens Rep. 2002 Apr;4(2):160-6
references.pmid: 11884272
references.citation: J Mol Med (Berl). 2001 Aug;79(8):449-58
references.pmid: 11511975
references.citation: Cardiovasc Drugs Ther. 2011 Oct;25(5):441-9
references.pmid: 21912849
references.citation: J Clin Hypertens (Greenwich). 2012 Apr;14(4):198-205
references.pmid: 22458740
references.citation: J Hypertens Suppl. 1992 Dec;10(7):S179-86
references.pmid: 1291652
references.citation: Diabetes Care. 2004 Jun;27(6):1487-95
references.pmid: 15161807
references.citation: Histochem Cell Biol. 2004 Oct;122(4):339-52
references.pmid: 15338229
references.citation: Atherosclerosis. 2005 Dec;183(2):349-54
references.pmid: 15899485
references.citation: Angiology. 1999 Apr;50(4):273-82
references.pmid: 10225462