Distribution of the Q192R polymorphism of the paraoxonase 1 gene in a population of the district of Junín (Junín region, Peru)

Authors

DOI:

https://doi.org/10.24265/horizmed.2017.v17n2.05

Keywords:

Paraoxonase, Polymorphism, Cardiovascular risk factor, Altitude

Abstract

Objective: Paraoxonase 1 (PON1), an esterase associated with high-density lipoproteins (HDL), has several polymorphisms: the PON1 Q192R polymorphism (coding region) is responsible for variations in the paraoxonase activity of the enzyme. The PON1 192R allele is considered a risk factor for developing cardiometabolic disorders in some populations. The aim of the present study is to determine the distribution of the PON1 Q192R polymorphism and its association with the lipid profile and APO A1 in an Andean population.

Materials and methods: A descriptive, cross-sectional study involving 79 healthy adults (26 males and 53 females), residents of the district of Junín at 4105 m.a.s.l. The PCR/RFLP technique was used for the analysis of the PON1 Q192R polymorphism. The serum values of the lipid profile and APO A1, and the paraoxonase and arylesterase activities of the enzyme were determined.

Results: The distribution of the genotypes for PON1192 was QQ 13.9%, QR 45.6% and RR 40.5%, and the most frequent allele was 192R 63%. The baseline and stimulated paraoxonase activities were different based on their genotypes, while the esterase activity of the enzyme was not influenced by the polymorphism. On the other hand, no association was found between the PON1 Q192R polymorphism and the lipid profile and APO A1.

Conclusions: The high prevalence of the PON1 192R allele among the studied population probably indicates an important role in the development of cardiometabolic diseases.

Downloads

Download data is not yet available.

References

Draganov DI, Teiber JF, Speelman A, Osawa Y, Sunahara R, La Du B. N. Human paraoxonases (PON 1, PON 2, and PON 3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res. 2005; 46(6):1239-47.

Mackness B, Durrington PN, Mackness MI. Human serum paraoxonase. Gen Pharmacol. 1998; 31(3):32936

Mackness MI, Arrol S, Durrington PN. Paraoxonase prevents accumulation of lipo-peroxides in low-density lipoprotein. FEBS Letts. 1991; 286(1):1524.

Watson AD, Berliner JA, Hama SY, La Du BN, Fault KF, Fogelman AM, et al. Protec¬tive effect of high density lipoprotein associated paraoxonase. Inhibition of the bio¬logical activity of minimally oxidized low-density lipoprotein. J Clin Invest. 1995; 96(6):288291.

Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest. 1998; 101(8):1581-90.

Deakin SP, Bioletto S, Bochaton-Piallat ML, James RW. HDL- associated paraoxonase-1 can redistribute to cell membranes and influence sensitivity to oxida¬tive stress. Free Radic Biol Med. 2011; 50(1):1029.

Goswami B, Tayal D, Gupta N, and Mallika V. Paraoxonase: a multifaceted biomolecule. Clin Chim Acta. 2009; 410(1):112.

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; 52(3): 598- 608.

Serrato M, Marian AJ. A variant of humanparaoxonase/ arylesterase (HUMPONA) gene is a risk factor for coronary artery disease. J Clin Invest 1995; 96(6): 30058

Mackness B. Mackness M, Aviram M, Paragh G. The Paraoxonases: Their Role in Disease Development and Xenobiotic Metabolism. Vol 3. The Netherlands: Springer, 2008. p. 5160

Wang M, Lang X, Zou L, Huang S, Xu Z. Four genetic polymorphisms of the paraoxonase gene and risk of coronary heart disease: a meta-analysis based on 88 casecontrol studies. Atherosclerosis. 2010; 214(2):377-85.

Williams L. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III) final report. Circulation. 2002; 106(25):3143-421.

Hernández AF, Gonzalvo MC, Gil L, Rodrigo L, Villanueva E, Pla A. Distribution profiles of paraoxonase and cholinesterase phenotypes in a Spanish population. Chem Biol Interact. 1999;119120: 201-209

Eckerson HW, Whyte CM, La Du BN. The human serum paraoxonase/ arylesterase polymorphism. Am. J. hum. Genet. 1983; 35(6):1126−38.

Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski C, Furlong C. The molecular basis of the human serum paraoxonase activity polymorphism. Nat Genet. 1993;3(1):73- 6.

Hassan MA, Al-Attas OS, Hussain T, Al-Daghri NM, Alokail MS, Mohammed AK, et al. The Q192R polymorphism of the paraoxonase 1 gene is a risk factor for coronary artery disease in Saudi subjects. Mol Cell Biochem. 2013;380(1-2):121-8

Wheeler JG, Keavney BD, Watkins H, Collins R, Danesh J. Four paraoxonase gene polymorphisms in 11212 cases of coronary heart disease and 12786 controls: meta-analysis of 43 studies. Lancet. 2004; 363(9410):68995.

Cataño HC, Cueva JL, Cardenas AM, Izaguirre V, Zavaleta AI, Carranza E, et al. Distribution of paraoxonase-1 gene polymorphisms and enzyme activity in a Peruvian population. Environ Mol Mutagen. 2006;47(9): 699706.

Hegele RA. Genetic prediction of atherosclerosis: Lessons from studies in native Canadian populations. Clin Chim Acta. 1999;286(1):47-61

Gamboa R, Zamora J, RodriguezPerez JM, Fragoso JM, Cardoso G, PosadasRomero C, et al: Distribution of paraoxonase PONÍ gene polymorphisms in Mexican populations. Its role in the lipid profile. Exp Mol Pathol. 2006; 80(1): 8590.

Scacchi R, Corbo RM, Rickards O, De Stefano GF. New data on the world distribution of paraoxonase (PON1 Gln 192 -- Arg) gene frequencies. Hum Biol. 2003;75(3):365-73.

Santos N, Ribeiro-dos-santos A, Santos S. Frequency of the Q192R and L55M polymorphisms of the human serum paraoxonase gene (PON1) in ten Amazonian Amerindian tribes. Genetics and Molecular Biology. 2005; 28(1): 369.

Sanghera D, Aston C, Saha N, Kamboh M. DNA polymorphism in two paraoxonase genes (PON1 and PON2) are associated with the risk of coronary heart disease. Am J Human Genet. 1998; 62(1):36-44

Sato H, Ito Y, Ueyama J, Kano Y, Arakawa T, Gotoh M, et al. Effects of Paraoxonase 1 gene polymorphisms on organophosphate insecticide metabolism in Japanese pest control workers. J Occup Health. 2016; 58(1): 5665

Pejin-Grubiša, I. HDL-Associated paraoxonase 1gene polymorphisms as genetic markers for wide spread diseases. In S. Frank and G. Kostner , Lipoproteins Role in Health and Disease. 2012, p. 431 44.

Hegele RA, Brunt JH, Connelly PW. A polymorphism of the paraoxonase gene associated with variation in plasma lipoproteins in a genetic isolate. Arterioscler Thromb Vasc Biol. 1995;15(1): 8995.

Agachan B, Yilmaz H, Karaali Z, Isbir T. Paraoxonase 55 and 192 polymorphism and its relationship to serum paraoxonase activity and serum lipids in Turkish patients with non-insulin dependent diabetes mellitus. Cell Biochem Funct. 2004; >22(3):1638

Ruiz J, Blanche H, James RW, Garin MC, Vaisse C, Charpentier G, et al. Gln-Arg 192 polymorphism of paraoxonase and coronary artery disease in type 2 diabetes. Lancet. 1995; 346:86972.

Senti M, Tomas M, Fitó M, Weinbrenner T, Covas MI, Sala J, et al. Antioxidant paraoxonase 1 activity in the metabolic syndrome. J Clin Endocrinol Metab. 2003; 88(11):5422-6

Segura L, Regulo C, Parodi J. Factores de Riesgo de las Enfermedades Cardiovasculares en el Perú. Estudio TORNASOL. Rev Peru Cardiol. 2006; 32(2):82-128.

West J, Schoene R, Luks A, Milledge J. High Altitude Medicine and Physiology. 5nd ed. CRC Press, Taylor & Francis Group Boca Raton, FL, 2013. p. 275-277

Published

2017-06-05

How to Cite

1.
Carranza Alva E, Peña Suasnábar C, Florentini Carranza A. Distribution of the Q192R polymorphism of the paraoxonase 1 gene in a population of the district of Junín (Junín region, Peru). Horiz Med [Internet]. 2017Jun.5 [cited 2025Jun.21];17(2):30-7. Available from: https://www.horizontemedico.usmp.edu.pe/index.php/horizontemed/article/view/578

Issue

Section

Original article

Most read articles by the same author(s)