• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Dec 1995; 96(6): 3005–3008.
PMCID: PMC186013

A variant of human paraoxonase/arylesterase (HUMPONA) gene is a risk factor for coronary artery disease.

Abstract

Coronary artery disease (CAD) is a complex trait caused by a number of genetic and environmental factors. Recently, paraoxonase/arylesterase (PONA) enzyme has been implicated in the pathogenesis of atherosclerosis. There is a 10-40-fold variability in the activity of this enzyme among individuals. This variability is due to the presence of an A/G polymorphism in the coding region of the gene (HUMPONA). The A and G alleles code for glutamine (A genotype) and arginine (B genotype), respectively. Individuals with A genotype have a lower enzymatic activity than those with B genotype. We determined the HUMPONA genotypes and alleles in 223 patients with angiographically documented CAD and in 247 individuals in the general population. The distribution of genotypes were in Hardy-Weinberg equilibrium in patients and in controls. Genotypes A and B were present in 120 (49%) and 28 (11%) individuals in controls and in 68 (30%) and 40 (18%) patients with CAD, respectively (chi squared= 16.5, P= 0.0003). The frequency of the A allele was 0.69 in controls and 0.56 in patients (OR= 1.7, P= 0.0001). There were no differences in the distribution of HUMPONA genotypes in the subgroups of patients with restenosis, myocardial infarction, or any of the conventional risk factors for CAD as compared with corresponding subgroups. In summary, variants of the HUMPONA gene are involved in predisposition to coronary atherosclerosis.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (747K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Marenberg ME, Risch N, Berkman LF, Floderus B, de Faire U. Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med. 1994 Apr 14;330(15):1041–1046. [PubMed]
  • Chamberlain JC, Galton DJ. Genetic susceptibility to atherosclerosis. Br Med Bull. 1990 Oct;46(4):917–940. [PubMed]
  • Lander ES, Schork NJ. Genetic dissection of complex traits. Science. 1994 Sep 30;265(5181):2037–2048. [PubMed]
  • Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S, et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature. 1992 Oct 15;359(6396):641–644. [PubMed]
  • Beohar N, Damaraju S, Prather A, Yu QT, Raizner A, Kleiman NS, Roberts R, Marian AJ. Angiotensin-I converting enzyme genotype DD is a risk factor for coronary artery disease. J Investig Med. 1995 Jun;43(3):275–280. [PubMed]
  • Mackness MI, Arrol S, Abbott CA, Durrington PN. Is paraoxonase related to atherosclerosis. Chem Biol Interact. 1993 Jun;87(1-3):161–171. [PubMed]
  • Mackness MI, Arrol S, Durrington PN. Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett. 1991 Jul 29;286(1-2):152–154. [PubMed]
  • McElveen J, Mackness MI, Colley CM, Peard T, Warner S, Walker CH. Distribution of paraoxon hydrolytic activity in the serum of patients after myocardial infarction. Clin Chem. 1986 Apr;32(4):671–673. [PubMed]
  • Furlong CE, Richter RJ, Seidel SL, Motulsky AG. Role of genetic polymorphism of human plasma paraoxonase/arylesterase in hydrolysis of the insecticide metabolites chlorpyrifos oxon and paraoxon. Am J Hum Genet. 1988 Sep;43(3):230–238. [PMC free article] [PubMed]
  • Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski CJ, Furlong CE. The molecular basis of the human serum paraoxonase activity polymorphism. Nat Genet. 1993 Jan;3(1):73–76. [PubMed]
  • Furlong CE, Costa LG, Hassett C, Richter RJ, Sundstrom JA, Adler DA, Disteche CM, Omiecinski CJ, Chapline C, Crabb JW, et al. Human and rabbit paraoxonases: purification, cloning, sequencing, mapping and role of polymorphism in organophosphate detoxification. Chem Biol Interact. 1993 Jun;87(1-3):35–48. [PubMed]
  • Adkins S, Gan KN, Mody M, La Du BN. Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respective A or B allozymes. Am J Hum Genet. 1993 Mar;52(3):598–608. [PMC free article] [PubMed]
  • Playfer JR, Eze LC, Bullen MF, Evans DA. Genetic polymorphism and interethnic variability of plasma paroxonase activity. J Med Genet. 1976 Oct;13(5):337–342. [PMC free article] [PubMed]
  • Marshall HW, Morrison LC, Wu LL, Anderson JL, Corneli PS, Stauffer DM, Allen A, Karagounis LA, Ward RH. Apolipoprotein polymorphisms fail to define risk of coronary artery disease. Results of a prospective, angiographically controlled study. Circulation. 1994 Feb;89(2):567–577. [PubMed]
  • Damaraju S, Yu QT, Safavi F, Marian AJ. Apolipoprotein epsilon 4 is not a genetic risk factor for coronary artery disease or restenosis after percutaneous transluminal coronary angioplasty. Am J Cardiol. 1995 Jun 1;75(16):1181–1183. [PubMed]
  • Katsuya T, Koike G, Yee TW, Sharpe N, Jackson R, Norton R, Horiuchi M, Pratt RE, Dzau VJ, MacMahon S. Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease. Lancet. 1995 Jun 24;345(8965):1600–1603. [PubMed]
  • Ishigami T, Umemura S, Iwamoto T, Tamura K, Hibi K, Yamaguchi S, Nyuui N, Kimura K, Miyazaki N, Ishii M. Molecular variant of angiotensinogen gene is associated with coronary atherosclerosis. Circulation. 1995 Feb 15;91(4):951–954. [PubMed]
  • Eriksson P, Kallin B, van 't Hooft FM, Båvenholm P, Hamsten A. Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1851–1855. [PMC free article] [PubMed]
  • Eckerson HW, Wyte CM, La Du BN. The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet. 1983 Nov;35(6):1126–1138. [PMC free article] [PubMed]
  • Kanemitsu S, Tekekoshi N, Murakami E. Effects of LDL apheresis on restenosis after angioplasty. Chem Phys Lipids. 1994 Jan;67-68:339–343. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • Gene
    Gene
    Gene links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene
    HomoloGene links
  • MedGen
    MedGen
    Related information in MedGen
  • OMIM
    OMIM
    OMIM record citing PubMed
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...