Investigation of PON 55 Gene Polymorphism Frequency in Patients with Hyperlipidemia
Özlem Yüksel 1, Recep Sütcü 2, İsmail Hakkı Ersoy 3, Hikmet Orhan 4
More Detail
1 Süleyman Demirel Üniversitesi Tıbbi Biyokimya AD Isparta
2 Katip Çelebi Üniversitesi Tıbbi Biyokimya AD İzmir
3 Isparta Devlet Hastanesi Endokrinoloji Kliniği, Isparta
4 Süleyman Demirel Üniversitesi Halk Sağlığı AD, Isparta
EUR J BASIC MED SCI, Volume 2, Issue 3, pp. 79-84.
https://doi.org/10.21601/ejbms/9184
OPEN ACCESS
ABSTRACT
Paraoxonase (PON1) is a calcium-dependent esterase that is a component of high density lipoprotein. PON1 serves as a protective factor against oxidative modification of LDL. Serum PON1 activity decreases with diseases related to lipid metabolism which increases risk of atherosclerosis. Research has focused on two polymorphisms. PON 55 L>M polymorphism which is one of two polymorphism effects concentration of paraoxonase because of connection to polymorphism on PON 1 promoter region. PON 55 L>M polymorphism located on PON1’s N-terminal region which has role to bind HDL. Many researches were carried out to investigate relationship between PON1 gene polymorphism and plasma lipoproteins. In this study, patients whose lipid profile measured in biochemistry laboratory are investigated. We examined amino acid changes at codon 55 in the PON1 gene by polymerase chain reaction and using restriction enzymes in 80 patients (26 men, 54 women; mean age 55.31±14.6 years) with high total cholesterol and LDL-C levels and in 60 patients (15 men, 45 women; mean age 42.75±17.7 years) with normal serum lipoprotein profile. Distribution of genotypes in the patient and control groups were 17.5% and 5% for MM, 40% and 51.7% for LM, 42.5% and 43.3% for LL, respectively. While the frequency of PON1 55M allele was higher in the patient group (0.375 vs.0.308), PON1 55 L allele frequency was higher in the control group. There was a marginal significant relationship between the PON1 M/L 55 polymorphism and hyperlipidemia (p=0.065). These data suggest that the PON1 M/L 55 polymorphism may show a significant relationship with hyperlipidemia.
CITATION
Yüksel Ö, Sütcü R, Ersoy İH, Orhan H. Investigation of PON 55 Gene Polymorphism Frequency in Patients with Hyperlipidemia. Eur J Basic Med Sci. 2012;2(3):79-84.
https://doi.org/10.21601/ejbms/9184
REFERENCES
- Antikainen M, Murtomäki S, Syvänne M, et al. The Gln-Arg191 polymorphism of the human paraoxonase gene (HUMPONA) is not associated with the risk of coronary artery disease in Finns. J Clin Invest 1996;98:883-5.
- La Du BN, Adkins S, Kuo CL, Lipsig D. Studies on human serum paraoxonase/arylesterase. Chem Biol Interact 1993;87:25-34.
- La Du BN. Structural and functional diversity of paraoxonases. Nat Med 1996;2:1186-7.
- Durrington PN, Mackness B, Mackness MI. Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol 2001; 21:473-80.
- Motti C, Dessì M, Gnasso A, et al. A multiplex PCR-based DNA assay for the detection of paraoxonase gene cluster polymorphisms. Atherosclerosis 2001;158:35-40.
- Aviram M. Does paraoxonase play a role in susceptibility to cardiovascular disease? Mol Med Today 1999; 5:381-6.
- Mackness MI, Durrington PN. HDL, its enzymes and its potential to influence lipid peroxidation. Atherosclerosis 1995;115:243-53.
- Sanghera DK, Saha N, Aston CE, Kamboh MI. Genetic polymorphism of paraoxonase and the risk of coronary heart disease. Arterioscler Thromb Vasc Biol 1997; 17:1067-73.
- Ruiz J, Blanché H, James RW, et al. Gln-Arg192 polymorphism of paraoxonase and coronary heart disease in type 2 diabetes. Lancet 1995;346:869-72.
- Serrato M, Marian AJ. A variant of human paraoxonase/arylesterase (HUMPONA) gene is a risk factor for coronary artery disease. J Clin Invest 1995;96:3005-8.
- Zama T, Murata M, Matsubara Y, et al. A 192Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese. Arterioscler Thromb Vasc Biol 1997;17:3565-9.
- Gupta N, Gill K, Singh S. Paraoxonases: Structure, gene polymorphism & role in coronary artery disease. Indian J Med Res 2009; 130(4):361-8.
- 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;3:73-6.
- Watson AD, Navab M, Hama SY, et al. Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein. J Clin Invest 1995;95:774-82.
- 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.
- Leviev I, Deakin S, James RW. Decreased stability of the M54 isoform of paraoxonase as a contributory factor to variations in human serum paraoxonase concentrations. J Lipid Res 2001;42(4):528-35.
- Leus FR, Zwart M, Kastelein JJ, Voorbij HA.PON2 gene variants are associated with clinical manifestations of cardiovascular disease in familial hypercholesterolemia patients. Atherosclerosis 2001;154:641–649.
- Fanella S, Harris SB, Young TK, et al. Association between PON1 L/M55 polymorphism and plasma lipoproteins in two Canadian aboriginal populations. Clin Chem Lab Med 2000; 38:413–420.
- Malin R, Laaksonen R, Knuuti J, et al. Paraoxonase genotype modifies the effect of pravastatin on high-density lipoprotein cholesterol. Pharmacogenetics 2001;11:625–633.
- Watzinger N, Schmidt H, Schumacher M, et al. Human paraoxonase1 gene polymorphisms and the risk of coronary heart disease: a community-based study. Cardiology 2002;98:116–122.
- Mackness B, Davies GK, Turkie W, et al. Paraoxonase status in coronary heart disease: are activity and concentration more important than genotype? Arterioscler Thromb Vasc Biol 2001;21:1451–7.
- Bonafe M, Marchegiani F, Cardelli M, et al. Genetic analysis of paraoxonase (PON1) locus reveals an increased frequency of Arg192 allele in centenarians. Eur J Hum Genet 2002;10:292–6.
- Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837–47.
- Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998, 339:229– 34.
- Stein E. The lower the beter? Reviewing the evidence for more aggressive cholesterol reduction and goal attainment. Atheroscler 2002 (Suppl):2;19-25.