© 1997 American Heart Association, Inc.
Articles |
A 192Arg Variant of the Human Paraoxonase (HUMPONA) Gene Polymorphism Is Associated With an Increased Risk for Coronary Artery Disease in the Japanese
From the Department of Medicine, School of Medicine, Keio University, the Second Department of Medicine, Kyorin University (K.K., N.A., H.Y., K.I.), and Hibiya Medical Center, Sakura Bank (G.W.), Tokyo, Japan.
Correspondence to Mitsuru Murata, MD, Department of Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160, Japan. E-mail murata{at}mc.med.keio.ac.jp
Abstract Recent reports have suggested that polymorphisms in the human paraoxonase (HUMPONA) gene may be a genetic risk factor for coronary artery disease (CAD) in white populations. However, this association has not yet been confirmed in other ethnic populations. We studied 75 Japanese patients with CAD, whose coronary lesions were confirmed by angiography, and 115 Japanese control subjects with no history of CAD and a normal resting electrocardiogram. The assays for genotyping the two polymorphisms in the HUMPONA gene (192Arg/Gln and 55Leu/Met) were based on changes in restriction enzyme digestion patterns. For codon 192, the frequencies of the Arg-coding allele (B allele) in both patients and control subjects were much higher than those from published results of whites (.26 to .31), and the difference between patients (.74) and control subjects (.59) was statistically significant (P=.002). The patient group had a higher proportion of Arg/Arg (B/B) homozygotes (52.0% vs 32.2%, P=.006). For codon 55, the frequencies of the Leu-coding allele in control subjects and patients were much higher (.91 and .93, respectively) than those published results for whites, but there was no difference between Japanese control subjects and Japanese patients. When subjects with the 55Leu/Leu genotype only were analyzed, 192Arg/Arg homozygotes were still significantly more frequent in the patients than in the control subjects (55.4% vs 37.2%, P=.024), and the frequency of the 192Arg allele was also higher in patients than control subjects (P=.013). Logistic regression analysis including conventional coronary risk factors revealed that 192Arg is an independent risk factor for CAD. Thus, in the Japanese, the association of CAD with the 192Arg variant of HUMPONA (B-type enzyme) is similar to that reported for whites, although the allele frequencies for 192Arg and 55Leu are much higher in the former than the latter population.
Key Words: paraoxonase • coronary artery disease • genetics • angiography • risk factors
This article has been cited by other articles:
 |
|
 |
|
  S. Lavi, J. P. McConnell, R. Lavi, G. W. Barsness, C. S. Rihal, G. D. Novak, L. O. Lerman, and A. Lerman Association Between the Paraoxonase-1 192Q>R Allelic Variant and Coronary Endothelial Dysfunction in Patients With Early Coronary Artery Disease Mayo Clin. Proc., February 1, 2008; 83(2): 158 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Browne, S. T. Koury, S. Marion, G. Wilding, P. Muti, and M. Trevisan Accuracy and Biological Variation of Human Serum Paraoxonase 1 Activity and Polymorphism (Q192R) by Kinetic Enzyme Assay Clin. Chem., February 1, 2007; 53(2): 310 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Kakafika, S. Xenofontos, V. Tsimihodimos, A. P. Tambaki, E. S. Lourida, R. Kalaitzidis, M. A. Cariolou, M. Elisaf, and A. D. Tselepis The PON1 M55L gene polymorphism is associated with reduced HDL-associated PAF-AH activity J. Lipid Res., October 1, 2003; 44(10): 1919 - 1926. [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]
|
|
|
|
|
|
X. Wang, Z. Fan, J. Huang, S. Su, Q. Yu, J. Zhao, R. Hui, Z. Yao, Y. Shen, B. Qiang, et al. Extensive Association Analysis Between Polymorphisms of PON Gene Cluster With Coronary Heart Disease in Chinese Han Population Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 328 - 334. [Abstract] [Full Text] [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]
|
|
|
|
 |
|
 S. Deakin, I. Leviev, V. Nicaud, M.-C. B. Meynet, L. Tiret, and R. W. James Paraoxonase-1 L55M Polymorphism Is Associated with an Abnormal Oral Glucose Tolerance Test and Differentiates High Risk Coronary Disease Families J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1268 - 1273. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Markus, Z. Kapozsta, R. Ditrich, C. Wolfe, N. Ali, J. Powell, M. Mendell, and M. Cullinane Increased Common Carotid Intima-Media Thickness in UK African Caribbeans and Its Relation to Chronic Inflammation and Vascular Candidate Gene Polymorphisms Stroke, November 1, 2001; 32(11): 2465 - 2471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Mackness, G. K. Davies, W. Turkie, E. Lee, D. H. Roberts, E. Hill, C. Roberts, P. N. Durrington, and M. I. Mackness Paraoxonase Status in Coronary Heart Disease: Are Activity and Concentration More Important Than Genotype? Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1451 - 1457. [Abstract] [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]
|
|
|
|
|
|
M. Senti, M. Tomas, J. Marrugat, R. Elosua, and f. t. REGICOR Investigators Paraoxonase1-192 Polymorphism Modulates the Nonfatal Myocardial Infarction Risk Associated With Decreased HDLs Arterioscler. Thromb. Vasc. Biol., March 1, 2001; 21(3): 415 - 420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. Sen-Banerjee, X. Siles, and H. Campos Tobacco Smoking Modifies Association Between Gln-Arg192 Polymorphism of Human Paraoxonase Gene and Risk of Myocardial Infarction Arterioscler. Thromb. Vasc. Biol., September 1, 2000; 20(9): 2120 - 2126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. James, I. Leviev, and A. Righetti Smoking Is Associated With Reduced Serum Paraoxonase Activity and Concentration in Patients With Coronary Artery Disease Circulation, May 16, 2000; 101(19): 2252 - 2257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Leviev and R. W. James Promoter Polymorphisms of Human Paraoxonase PON1 Gene and Serum Paraoxonase Activities and Concentrations Arterioscler. Thromb. Vasc. Biol., February 1, 2000; 20(2): 516 - 521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Aubo, M Senti, J Marrugat, M Tomas, J Vila, J Sala, and R Masia Risk of myocardial infarction associated with Gln/Arg 192 polymorphism in the human paraoxonase gene and diabetes mellitus Eur. Heart J., January 1, 2000; 21(1): 33 - 38. [Abstract] [PDF]
|
|
|
|
|
|
R. C. Sorenson, C. L. Bisgaier, M. Aviram, C. Hsu, S. Billecke, and B. N. La Du Human Serum Paraoxonase/Arylesterase's Retained Hydrophobic N-Terminal Leader Sequence Associates With HDLs by Binding Phospholipids : Apolipoprotein A-I Stabilizes Activity Arterioscler. Thromb. Vasc. Biol., September 1, 1999; 19(9): 2214 - 2225. [Abstract] [Full Text] [PDF]
|
|