This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schmidt, H. Articles by Kostner, G. M. Search for Related Content PubMed PubMed Citation Articles by Schmidt, H. Articles by Kostner, G. M.

(Stroke. 1998;29:2043-2048.)
© 1998 American Heart Association, Inc.

Original Contributions

Paraoxonase PON1 Polymorphism Leu-Met54 Is Associated With Carotid Atherosclerosis

Results of the Austrian Stroke Prevention Study

Helena Schmidt, MD; Reinhold Schmidt, MD; Kurt Niederkorn, MD; Anita Gradert; Martin Schumacher, MD; Norbert Watzinger, MD; Hans-Peter Hartung, MD; Gert M. Kostner, PhD

From the Institute for Medical Biochemistry (H.S., A.G., G.M.K.), the Department of Neurology (R.S., K.N., N.W., H.-P.H.), and the Department of Internal Medicine (M.S.), Karl-Franz University, Graz, Austria.

Correspondence to Helena Schmidt, MD, Institute for Medical Biochemistry, Karl-Franz University Graz, Harrachgasse 21 A-8010 Graz, Austria. E-mail helena.schmidt{at}kfunigraz.ac.at

Background and Purpose—Genetic polymorphism at the paraoxonase locus is associated with serum concentration and activity of paraoxonase and with increased risk for coronary heart disease. Two frequent polymorphisms present at the paraoxonase gene are the methionine (M allele) leucine (L allele) interchange at position 54 and the arginine (B allele) glutamine (A allele) interchange at position 191. This is the first study to determine the effect of these polymorphisms on carotid atherosclerosis.

Methods—The paraoxonase genotypes at positions 54 and 191 of 316 randomly selected individuals aged 44 to 75 years were determined by polymerase chain reaction–based restriction enzyme digestion. Carotid atherosclerosis was assessed by color-coded Duplex scanning and was graded on a 5-point scale ranging from 0 (normal) to 5 (complete luminal obstruction).

Results—The LL, LM, and MM genotypes at position 54 were noted in 137 (43.4%), 132 (41.8%), and 47 (14.9%) subjects; the AA, AB, and BB genotypes at position 191 occurred in 172 (54.4%), 124 (39.2%), and 20 (6.3%) individuals. The LL genotype was significantly associated with the presence and severity of carotid disease (P=0.022), whereas the 191 polymorphism had no effect. Logistic regression analysis with age and sex forced into the model demonstrated plasma fibrinogen (odds ratio [OR], 1.005 per mg/dL), LDL cholesterol (OR, 1.01 per mg/dL), cardiac disease (OR, 1.75), and the paraoxonase LL genotype to be significant predictors of carotid atherosclerosis. The ORs for the associations with age and sex were 1.09 (P=0.0003) and 1.66 (P=0.052) per year.

Conclusions—These data suggest that the paraoxonase LL genotype may represent a genetic risk factor for carotid atherosclerosis.

Key Words: atherosclerosis • carotid arteries • genetics • paraoxonase

This article has been cited by other articles:

				C. S. Carlson, P. J. Heagerty, T. S. Hatsukami, R. J. Richter, J. Ranchalis, J. Lewis, T. J. Bacus, L. A. McKinstry, G. D. Schellenberg, M. Rieder, et al. TagSNP analyses of the PON gene cluster: effects on PON1 activity, LDL oxidative susceptibility, and vascular disease J. Lipid Res., May 1, 2006; 47(5): 1014 - 1024. [Abstract] [Full Text] [PDF]

				T. M. van Himbergen, M. Roest, J. de Graaf, E. H. J. M. Jansen, H. Hattori, J. J. P. Kastelein, H. A. M. Voorbij, A. F. H. Stalenhoef, and L. J. H. van Tits Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia J. Lipid Res., March 1, 2005; 46(3): 445 - 451. [Abstract] [Full Text] [PDF]

				T. A. Manolio, E. Boerwinkle, C. J. O'Donnell, and A. F. Wilson Genetics of Ultrasonographic Carotid Atherosclerosis Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1567 - 1577. [Abstract] [Full Text] [PDF]

				G. P. Jarvik, T. S. Hatsukami, C. Carlson, R. J. Richter, R. Jampsa, V. H. Brophy, S. Margolin, M. Rieder, D. Nickerson, G. D. Schellenberg, et al. Paraoxonase Activity, But Not Haplotype Utilizing the Linkage Disequilibrium Structure, Predicts Vascular Disease Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): 1465 - 1471. [Abstract] [Full Text] [PDF]

				C. S. Fox, J. F. Polak, I. Chazaro, A. Cupples, P. A. Wolf, R. A. D'Agostino, and C. J. O'Donnell Genetic and Environmental Contributions to Atherosclerosis Phenotypes in Men and Women: Heritability of Carotid Intima-Media Thickness in the Framingham Heart Study Stroke, February 1, 2003; 34(2): 397 - 401. [Abstract] [Full Text] [PDF]

				C. Kluft, R. Kleemann, and M.P.M. de Maat How best to counteract the enemies? By controlling inflammation in the coronary circulation Eur. Heart J. Suppl., November 1, 2002; 4(suppl_G): G53 - G65. [Abstract] [PDF]

				G. P. Jarvik, N. T. Tsai, L. A. McKinstry, R. Wani, V. H. Brophy, R. J. Richter, G. D. Schellenberg, P. J. Heagerty, T. S. Hatsukami, and C. E. Furlong Vitamin C and E Intake Is Associated With Increased Paraoxonase Activity Arterioscler. Thromb. Vasc. Biol., August 1, 2002; 22(8): 1329 - 1333. [Abstract] [Full Text] [PDF]

				L. A. Lange, D. W. Bowden, C. D. Langefeld, L. E. Wagenknecht, J. J. Carr, S. S. Rich, W. A. Riley, and B. I. Freedman Heritability of Carotid Artery Intima-Medial Thickness in Type 2 Diabetes Stroke, July 1, 2002; 33(7): 1876 - 1881. [Abstract] [Full Text] [PDF]

				B. Voetsch, K. S. Benke, B. P. Damasceno, L. H. Siqueira, and J. Loscalzo Paraoxonase 192 Gln->Arg Polymorphism: An Independent Risk Factor for Nonfatal Arterial Ischemic Stroke Among Young Adults Stroke, June 1, 2002; 33(6): 1459 - 1464. [Abstract] [Full Text] [PDF]

				M. M. Murphy, E. Vilella, S. Ceruelo, L. Figuera, M. Sanchez, J. Camps, G. Cuco, N. Ferre, A. Labad, N. Tasevska, et al. The MTHFR C677T, APOE, and PON55 Gene Polymorphisms Show Relevant Interactions with Cardiovascular Risk Factors Clin. Chem., February 1, 2002; 48(2): 372 - 375. [Full Text] [PDF]

				P. N. Durrington, B. Mackness, and M. I. Mackness Paraoxonase and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., April 1, 2001; 21(4): 473 - 480. [Abstract] [Full Text] [PDF]

				S. Billecke, D. Draganov, R. Counsell, P. Stetson, C. Watson, C. Hsu, and B. N. L. Du Human Serum Paraoxonase (pon1) Isozymes Q and R Hydrolyze Lactones and Cyclic Carbonate Esters Drug Metab. Dispos., November 1, 2000; 28(11): 1335 - 1342. [Abstract] [Full Text]

				G. P. Jarvik, L. S. Rozek, V. H. Brophy, T. S. Hatsukami, R. J. Richter, G. D. Schellenberg, and C. E. Furlong Paraoxonase (PON1) Phenotype Is a Better Predictor of Vascular Disease Than Is PON1192 or PON155 Genotype Arterioscler. Thromb. Vasc. Biol., November 1, 2000; 20(11): 2441 - 2447. [Abstract] [Full Text] [PDF]

				R. Schmidt, H. Schmidt, F. Fazekas, P. Kapeller, G. Roob, A. Lechner, G. M. Kostner, and H.-P. Hartung MRI Cerebral White Matter Lesions and Paraoxonase PON1 Polymorphisms : Three-Year Follow-Up of the Austrian Stroke Prevention Study Arterioscler. Thromb. Vasc. Biol., July 1, 2000; 20(7): 1811 - 1816. [Abstract] [Full Text] [PDF]