Study of Paraoxonase -1 Gene Polymorphism in a Healthy Population of Khorramabad, Iran

Document Type: Original Article

Authors

1 Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran

2 Department of Biology, Faculty of Science, Lorestan University, Khorrtamabad, Iran

3 Department of Agronomy and Plant Breeding, Faculty of Agriculture, Lorestan University, Khorramabad, Iran

4 Department of Pathology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran

Abstract

Human serum paraoxonase (HuPON1: EC 3.1.8.1), a calcium-dependent esterase, is synthesized in the liver and widely distributed in tissues including liver, kidney, intestine, and serum, where it is associated exclusively with high-density lipoprotein.  Human paraoxonase-1 plays an important role in prevention of atherosclerosis and also protection against organophosphate-induced neurotoxicity. Paraoxonase-1 shows 2 common polymorphisms: Q/R at position 192 and M/L at position 55. In this study, paraoxonase-1 192 and 55 polymorphisms were investigated in 64 healthy Iranian individuals. Genomic DNA was isolated from whole blood by the Bartlett method, and paraoxonase-1 genotypes were determined by polymerase chain reaction amplification followed by restriction isotyping and gel electrophoresis. The chi-square test was used to evaluate the Hardy-Weinberg equilibrium. The genotype frequencies for paraoxonase 1-Q192R­ were pproximately 47% (QQ), 41% (QR) and 12% (RR) and for paraoxonase-1 M55L, 44% (LL), 44% (ML) and 12% (MM). Thus, the frequency of alleles R, L, Q, and M were 0.33, 0.66, 0.67, and 0.34 respectively. In conclusion, the frequencies of paraoxonase-1 192 and 55 polymorphisms in this group of Iranian population were different from those seen in other Asian populations from Japan and China but similar to European (Caucasians).

Keywords


  1. Furlong, C.E., Cole, T.B., Jarvik, G.P., Costa, L.G., Pharmacogenomic considerations of the paraoxonase polymorphisms. Pharmacogenomics, 2002, Vol. 3(3), pp. 341-348.
  2. Hassett, C., Richter, R.J., Humbert, R., Chapline, C., Crabb, J.W., Omiecinski, C.J., et al. Characterization of Cdna Clones Encoding Rabbit and Human Serum Paraoxonase - the Mature Protein Retains Its Signal Sequence. Biochem, 1991, Vol. 30(42), pp. 10141-10149.
  3. Mackness, M.I., Esterases: Enzymes looking for a role?. Biochem Pharmacol, 1989, Vol. 38(3), pp. 385-390.
  4. Aviram, M., Rosenblat, M., Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radical Bio Med, 2004, Vol. 37(9), pp. 1304-1316.
  5. Furlong, C.E., Richter, R.J., Chapline, C., Crabb, J.W., Purification of Rabbit and Human Serum Paraoxonase. Biochem, 1991, Vol. 30(42), pp. 10133-10140.
  6. Costa, L.G., Cole, T.B., Jarvik, G.P., Furlong, C.E., Functional genomics of the paraoxonase (PON1) polymorphisms: Effects on pesticide sensitivity, cardiovascular disease, and drug metabolism. Annual Review of Medicine-Selected Topics in the Clinical Sciences, 2003, Vol. 54, pp. 371-392.
  7. Billeclke, S., Draganov, D., Counsell, R., Stetson, P., Watson, C., La, B.N., Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos, 2000, Vol. 28(11), pp. 1335-1342.
  8. jakubowski, H., Calcium-dependent human serum homocysteinethiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J Biol Chem, 2000, Vol. 275, pp. 3962-3975.
  9. Himbergen, T.M., Roest, M., Graaf, J., Jansen, E.H.J.M., Hattori, H., Kastelein, J.J.P., et al. Indications that paraoxonase-1 contributes to plasma high density lipoprotein levels in familial hypercholesterolemia. J Lipid Res, 2005, Vol. 46(3), pp. 445-451.
  10. Obata, T., Ito, T., Yonemura, A., Ayaori, M., Nakamura, H.F.O.,   R192Q paraoxonase gene variant is associated with a change in HDL-cholesterol level during dietary caloric restriction in nondiabetic healthy males. J Atheroscler Thromb, 2003, Vol. 10, pp. 57-62.
  11. Voetsch, B., Benke, K.S., Damasceno, B.P., Siqueira, L.H., Loscalzo, J., Paraoxonase 192 Gln-Arg polymorphism - An independent risk factor for nonfatal arterial ischemic stroke among young adults. Stroke, 2002, Vol. 33(6), pp. 1459-1464.
  12. Schmidt, R., Schmidt, H., Fazekas, F., Kapeller, P., Roob, G., Lechner, A., et al. MRI cerebral white matter lesions and paraoxonase PON1 polymorphisms - Three-year follow-up of the Austrian stroke prevention study. Arterioscler Thromb Vasc Biol, 2000, Vol. 20(7), pp. 1811-1816.
  13. Mackness, B., Durrington PN, Mackness MI. Polymorphisms of paraoxonase genes and low-density lipoprotein lipid peroxidation. Lancet, 1999, Vol. 6, pp. 468-469.
  14. Leviev, I., Negro, F., James, R.W., Two alleles of the human paraoxonase gene produce different amounts of mRNA - An explanation for differences in serum concentrations of paraoxonase associated with the (Leu-Met54) polymorphism. Arterioscler Thromb Vasc Biol, 1997, Vol. 17(11), pp. 2935-2939.
  15. Blatter-Garin, M.C., James, R.W., Dussoix, P., Blanche, H., Passa, P., Froguel, P., et al. Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of theenzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular diseasein diabetes. J Clin Invest. 1997, Vol. 99, pp. 62-66.
  16. Leviev, I., James, R.W., Promoter polymorphisms of human paraoxonase PON1 gene and serum paraoxonase activities and concentrations. Arterioscler Thromb Vasc Biol, 2000, Vol. 20(2). Pp. 516-521.
  17. Durrington, P.N., Mackness, B., Mackness, M.I., Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol, 2001, Vol. 21(4), pp. 473-480.
  18. Ng, C.J., Shih, D.M., Hama, S.Y., Villa, N., Navab, M., Reddy, S.T., The paraoxonase gene family and atherosclerosis. Free Radical Biology and Medicine, 2005, Vol. 15; 38(2), pp. 153-163.
  19. Bartlett, J.M.S., Stirling, D., PCR protocols: Humana Press; 2003.
  20. Humbert, R., Adler, D.A., Disteche, C.M., Hassett, C., Omiecinski, C.J., Furlong, C.E., The Molecular-Basis of the Human Serum Paraoxonase Activity Polymorphism. Nat Genet, 1993, Vol. 3(1), pp. 73-76.
  21. Adkins, S., Gan, K.N., Mody, M., La, D.B.N., Molecular basis for the polymorphic forms of human serum paraoxonase/arylesterase: Gln or Arg at position 192, for the respective A or B allozymes. Am J Hum Genet, 1991, Vol. 40, pp.  277-282.
  22. Sepahvand, F., Rahimi-Moghaddam, P., Shafiei, M., Ghaffari S.M., Rostam-Shirazi, M., Mahmoudian, M., Frequency of Paraoxonase 192/55 Polymorphism in an Iranian Population. J Tox Env Health, Part A., 2007, Vol. 70(13), pp. 1125-1129.
  23. Wang, X., Fan, Z., Huang, J., Su, S., Yu, Q., Zhao, J., et al. Extensive Association Analysis Between Polymorphisms of PON Gene Cluster With Coronary Heart Disease in Chinese Han Population. Arterioscler Thromb Vasc Biol, 2003, Vol. 23(2), pp. 328-334.
  24. Suehiro, T., Nakamura, T., Inoue, M., Shiinoki, T., Ikeda, Y., Kumon, Y., et al. A polymorphism upstream from the human paraoxonase (PON1) gene and its association with PON1 expression. Atherosclerosis, 2000, Vol, 150(2), PP. 295-298.
  25. Sardo, M.A, Campo, S., Bonaiuto, M., Bonaiuto, A., Saitta, C., Trimarchi, G., et al. Antioxidant effect of atorvastatin is independent of PON1 gene T(–107)C, Q192R and L55M polymorphisms in hypercholesterolaemic patients. Curr Med Res Opin, 2005, Vol. 21(5), pp. 777-784.
  26. Parra, S., Alonso-Villaverde. C., Coll, B., Marsillach, J., Aragon, G., et al. Serum paraoxonase-1 activity and concentration are influenced by human immunodeficiency virus infection. Atherosclerosis, 2007, Vol. 194(1), pp. 175-181.
  27. Clarimon, J., Eerola, J., Hellstrom, I., Tienari, P.J., Singleton., A., Paraoxonase 1 (PON1) gene polymorphisms and Parkinson's disease in a Finnish population. Neurosci Lett, 2004, Vol. 367(2), pp. 168-170.
  28. Gaidukov, L., Rosenblat, M., Aviram, M., Tawfik, D.S., The 192R/Q polymorphs of serum paraoxonase PON1 differ in HDL binding, lipolactonase stimulation, and cholesterol efflux. J Lipid Res, 2006, Vol. 47(11), pp. 2492-2502.