Paraoxonase (PON1) is a serum esterase responsible for the protection against xenobiotics toxicity such as paraoxon. Alterations in PON1 concentrations have been reported in a variety of diseases including diabetes mellitus (DM). It has been shown that the serum PON1 concentration and activity are decreased in patients with both type 1 and type 2 DM. This study aimed to investigate the lipid profiles and the relationship between PON1 activity and PON1, QR192 and LM55 polymorphisms in Turkish type 2 diabetic patients and non-diabetic control subjects. According to our results, RR variant had significantly higher PON activity than QQ and QR variants (p < 0.01) and LL variant had significantly higher PON activity than MM variant in both control and patient groups (p < 0.05). In conclusion, we found that PON1 192RR and 55LL genotypes are associated with higher PON activity than QQ and MM genotypes. This may be more protective to lipid peroxidation.
AbbottCAMacknessMIKumarSBoultonAJDurringtonPN (1995) Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins, Arteriosclerosis Thrombosis and Vascular Biology15: 1812–1818.
2.
AdkinsSGanKNModyMLa DuBN (1993) Molecular basis for the polymorphic forms of human serum paraoxonase/Arylesterase: glutamine or arginine at position 191, for the respective A or B allosymes. The American Journal of Human Genetics52:598–608.
3.
AgachanBYilmazHKaraaliZİsbirT (2004) 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 Biochemistry and Function22: 163–168.
4.
AviramMRosenblatMBisgaierCLNewtonRSPrimo-ParmoSLLA DuBN (1998) Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. Journal of Clinical Investigation101:1581–1590.
5.
BilleckeSDraganovDCounsellRStetsonPWatsonCHsuCLa DuBN (2000) Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metabolism and Disposition28: 1335–1342.
6.
Blatter-GarinMCJamesRWDussoixPBlancheHRuizJ (1997) Paraoxonase polymorphism Met-Leu54 is associated with modified concentrations of the enzyme. The Journal of Clinical Investigation99:62–66.
7.
BoemiMLevievISirollaCPieriCMarraMJamesRW (2001) Serum paraoxonase is reduced in type 1 diabetic patients compared to non-diabetic, first degree relatives; influence on the ability of HDL to protect LDL from oxidation. Atherosclerosis155: 229–235.
8.
CampsJMarsillachJJovenJ (2009) The paraoxonases: role in human diseases and methodological difficulties in measurement. Critical Reviews in Clinical Laboratory Sciences46: 83–106.
9.
DaviesHGRichterRJKeiferMBroomfieldCASowallaJFurlongCE (1996) The effect of the human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin. Nature Genetics14: 334–336.
10.
EckersonHWWyteCLa DuBN (1983) The human serum paraoxonase/arylesterase polymorphism. American Journal of Human Genetics35: 1126–1138.
11.
FerreNTousMPaulAZamoraAVendrellJJBardajiA, (2002) Paraoxonase Gln-Arg (192) and Leu-Met (55) gene polymorphisms and enzyme activity in a population with a low rate of coronary heart disease. Clinical Biochemistry35:197–203.
12.
FlekačMŠkrhaJZidkováKLacinováZHilgertováJ (2008) Paraoxonase 1 gene polymorphisms and enzyme activities in diabetes mellitus. Physiological Research57: 717–726.
13.
GrossERLadisaJFJrWeichrauchDOlsonLEKressTTHettrickDA, (2003) Reactive oxygen species modulate coronary wall shear stress and endothelial function during hyperglycemia. American Journal of Physiology284: H1552–H1559.
HoferSEBennettsBChanAKHollowayBKarschimkusCJenkinsAJ, (2006) Association between PON1 polymorphisms, PON activity and diabetes complications. Journal of Diabetes and Its Complications20:322–328.
16.
HumbertRAdlerDADistecheCMHassettCOmiecinskiCJFurlongCE (1993) The molecular basis of the human serum paraoxonase activity polymorphism. Nature Genetics3:73–76.
17.
KalousováMZimaTTesařVDusilová-SulkováSŠkrhaJ (2005) Advanced glycoxidation and products in chronic disease-clinical chemistry and genetic background. Mutation Research579: 37–46.
18.
KarabinaSALehnerANFrankEHarthasarathySSantanamN (2005) Oxidative inactivation of paraoxonase implications in diabetes mellitus and atherosclerosis. Biochimica et Biophysica Acta1725: 213–221.
19.
KodaYTachidaHSoejimaMTakenakaOKimuraH (2004) Population differences in DNA sequence variation and linkage disequilibrium at the PON1 gene. Annals of Human Genetics68: 110–119.
20.
LiBSedláčekMManoharanIBoopathyRDuysenEGMassonPLockridgeO (2005) Butyrylcholinesterase, paraoxonase and albumin esterase but not carboxylesterase are present in human plasma. Biochemical Pharmacology70: 1673–1684.
21.
LottiM (2000) Organophosphorus compounds. In: SpencerPSSchaumburgHLudolphAC (eds.) Experimental and Clinical Neurotoxicology. Oxford University Press, Oxford, 898–925.
22.
MacknessBDurringtonPNPoveyAThomsonSDippnallMMacknessMI, (2003) Paraoxonase and susceptibility to organophosporus poisoning in farmers dipping sheep. Pharmacogenetics13: 81–88.
23.
MacknessBMacknessMIArrolSTurkieWDurringtonPN (1998) Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high-density lipoprotein against low-density lipoprotein oxidative modification. FEBS Letters423: 57–60.
24.
MacknessMIHartyDBhatnagarD, (1991) Serum paraoxonase activity in familial hypercholesterolaemia and insulin dependent diabetes mellitus. Atherosclerosis86: 193–199.
25.
MacknessMIMacknessBDurringtonPNConellyPWHegeleRA (1996) Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins. Current Opinion in Lipidology7: 60–76.
26.
MarsillachJParraSFerreNCollBAlonso-VillaverdeCJovenJCampsJ (2008) paraoxonase-1 in chronic liver diseases, neurological diseases, and HIV infection. In MacknessBMacknessMAviramMParaghG (eds) The Paraoxonases: Their Role in Disease Development and Xnobiotic Metabolism. Dordrecht: Springer , 187–198.
27.
WatsonADBerlinerJAHamaSYLa DuBNFaullKFFogelmanAMNavabM (1995) Protective effect of high-density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimal oxidized low-density lipoprotein. The Journal of Clinical Investigation96: 2882–2891.
28.
WHO Consultation Report (1999) Definition, diagnosis and classification of Diabetes Mellitus and its complications, WHO, Geneva.
