Abstract
Paraoxonase (PON1) hydrolyzes paraoxon (PO) and diazoxon (DZO), active metabolites of insecticides parathion and diazinon. The PON1 gene has single nucleotide polymorphisms (SNPs) including a codon 192 arginine (R) to glutamine (Q) and methionine (M) to leucine (L) at codon 55. Hydrolysis of PO (POase), DZO (DZOase), dihydrocoumarin (lactonase), and phenyl acetate (arylesterase) were evaluated for associations with race, gender, age, and PON1 55/192 SNP genotypes. Variables were analyzed both individually and in combination. QQ individuals had higher lactonase (p < 0.001) than RR individuals. This might partially explain why predominantly RR African Americans have higher rates of coronary disease than predominantly QQ Caucasians. Significant (p < 0.001) differences in arylesterase were seen among genotypes with QQ and MM lowest whereas RR and LL were highest. This opposes the prevailing belief that arylesterase is unaffected by genotype and suggests that this activity cannot be used to quantify PON1 protein.
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Agachan B, Yilmaz H, Karaali Z, Isbir T (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 Biochem Funct 22:163–168
Aldridge WN (1953a) Serum esterases, I: two types of esterase (A and B) hydrolysing p-nitrophenyl acetate, propionate and butyrate, and a method for their determination. Biochem J 53:110–117
Aldridge WN (1953b) Serum esterases, II: an enzyme hydrolysing diethyl p-nitrophenyl phosphate (E600) and its identity with the A-esterase of mammalian sera. Biochem J 53:117–124
Allebrandt KV, Souza RLR, Chautard-Freire-Maia EA (2002) Variability of the paraoxonase gene (PON1) in Euro- and Afro-Brazilians. Toxicol Appl Pharmacol 180:151–156
Aviram M (2004) Introduction to the serial review on paraoxonases, oxidative stress, and cardiovascular diseases. Free Radic Biol Med 37:1301–1303
Aviram M, Billecke S, Sorenson R, Bisgaier C, Newton R, Rosenblat M, Erogul J, Hsu C, Dunlop C, La Du B (1998) Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different from that required for its arylesterase/paraoxonase activities: selective action of human paraoxonase allozymes Q and R. Arterioscler Thromb Vasc Biol 18:1617–1624
Aviram M, Hardak E, Vaya J, Mahmood S, Milo S, Hoffman A, Billecke S, Draganov D, Rosenblat M (2000) Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities. Circulation 101:2510–2517
Beekhof PK, Gorshunska M, Jansen EHJM (2012) Long-term stability of paraoxonase-1 and high-density lipoprotein in human serum. Lipids Health Dis 11:53–55
Ben-David M, Elias M, Filippi J-J, Duñach E, Silman I, Sussman JL, Tawfik DS (2012) Catalytic versatility and backups in enzyme active sites: the case of serum paraoxonase 1. J Mol Biol 418:181–196
Billecke S, Draganov D, Counsell R, Stetson P, Wayson C, Hsu C, La Du BN (2000) Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos 28:1335–1342
Blatter Garin MC, James RW, Dussoix P, Blanché H, Passa P, Froguel P, Ruiz J (1997) Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme: a possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes. J Clin Invest 99:62–66
Brophy VH, Jampsa RL, Clendenning JB, McKinstry LA, Jarvik GP, Furlong CE (2001) Effects of 5′ regulatory-region polymorphisms on paraoxonase-gene (PON1) expression. Am J Hum Genet 68:1428–1436
Cakatay U, Kayali R, Uzun H (2008) Relation of plasma protein oxidation parameters and paraoxonase activity in the ageing population. Clin Exp Med 8:51–57
Chambers JE, Chambers HW (1990) Time course of inhibition of acetylcholinesterase and aliesterases following parathion and paraoxon exposures in rats. Toxicol Appl Pharmacol 103:420–429
Chen J, Kumar M, Chan W, Berkowitz G, Wetmur JG (2003) Increased influence of genetic variation on PON1 activity in neonates. Environ Health Perspect 111:1403–1408
Cherki M, Berrougui H, Isabelle M, Cloutier M, Koumbadinga GA, Khalil A (2007) Effect of PON1 polymorphism on HDL antioxidant potential is blunted with aging. Exp Gerontol 42:815–824
Coombes RH, Crow JA, Dail MB, Chambers HW, Wills RW, Bertolet BD, Chambers JE (2011) Relationship of human paraoxonase-1 serum activity and genotype with atherosclerosis in individuals from the Deep South. Pharmacogenet Genomics 21:867–875
Costa LG, Vitalone A, Cole TB, Furlong CE (2005) Modulation of paraoxonase (PON1) activity. Biochem Pharmacol 69:541–550
Costa LG, Giordano G, Furlong CE (2011) Pharmacological and dietary modulators of paraoxonase 1 (PON1) activity and expression: the hunt goes on. Biochem Pharmacol 81:337–344
Davis KA, Crow JA, Chambers HW, Meek EC, Chambers JE (2009) Racial differences in paraoxonase-1 (PON1): a factor in the health of Southerners? Environ Health Perspect 117:1226–1231
Deakin SP, James RW (2004) Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci 107:435–447
Draganov DI (2010) Lactonases with organophosphate activity: structural and evolutionary perspectives. Chem Biol Interact 187:370–372
Durrington PN, Mackness B, Mackness MI (2001) Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol 21:473–480
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2013) Heart disease and stroke statistics, 2013 update: a report from the American Heart Association. Circulation 127:e6-e245
Hussein Y, Gharib A, Etewa R, ElSawy W (2011) Association of L55M and Q192R polymorphisms in paraoxonase 1 (PON1) gene with breast cancer risk and their clinical significance. Mol Cell Biochem 351:117–123
Jarvik GP, Rozek LS, Brophy VH, Hatsukami TS, Richter RJ, Schellenberg GD, Furlong CE (2000) Paraoxonase (PON1) phenotype is a better predictor of vascular disease than is PON1 192 or PON1 55 genoypte. Arterioscler Thromb Vasc Biol 20:2441–2447
Kim DS, Burt AA, Ranchalis JE, Richter RJ, Marshall JK, Eintracht JF, Rosenthal EA, Furlong CE, Jarvik GP (2012) Additional common polymorphisms in the PON gene cluster predict PON1 activity but not vascular disease. J Lipids. doi:10.1155/2012/476316
La Du BN, Adkins S, Kuo C-L, Lipsig D (1993) Studies on human serum paraoxonase/arylesterase. Chem Biol Interact 87:25–34
Leviev I, James RW (2000) Promoter polymorphisms of human paraoxonase PON1 gene and serum paraoxonase activities and concentrations. Arterioscler Thromb Vasc Biol 20:516–521
Mackness M, Mackness B (2004) Paraoxonase 1 and atherosclerosis: is the gene or the protein more important? Free Radic Biol Med 37:1317–1323
Mackness MI, Arrol S, Durrington PN (1991) Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett 286:152–154
Mackness B, Mackness MI, Arrol S, Turkie W, Julier K, Abuahsa B, Miller JE, Boulton AJM, Durrington PN (1998) Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus. Atherosclerosis 139:341–349
Marsillach J, Aragonès G, Beltrán R, Caballeria J, Pedro-Botet J, Morcillo-Suárez C, Navarro A, Joven J, Camps J (2009) The measurement of lactonase activity of paraoxonase-1 in the clinical evaluation of patients with chronic liver impairment. Clin Biochem 42:91–98
Mazur A (1946) An enzyme in animal tissues capable of hydrolyzing the phosphorus–fluorine bond of alkyl fluorophosphates. J Biol Chem 164:271–289
Mehdi MM, Rizvi SI (2012) Human plasma paraoxonase 1 (PON1) arylesterase activity during aging: correlation with susceptibility of LDL oxidation. Arch Med Res 43:438–443
Mehdi MM, Rizvi SI (2013) Plasma protein hydroperoxides during aging in humans: correlation with paraoxonase 1 (PON1) arylesterase activity and plasma total thiols. Arch Med Res 44:136–141
Milochevitch C, Khalil A (2001) Study of the paraoxonase and platelet-activating factor acetylhydrolase activities with aging. Prostaglandins Leukot Essent Fat Acids 65:241–246
Oliveira SA, Ribeiro CC, Ramires JA, Annichino-Bizzacchi JM (2004) PON1 M/L55 mutation protects high-risk patients against coronary heart disease. Int J Cardiol 94:73–77
Phuntuwate W, Suthisisang C, Koanantakul B, Mackness MI, Mackness B (2005) Paraoxonase 1 status in the Thai population. J Hum Genet 50:293–300
Rainwater DL, Rutherford S, Dyer TD, Rainwater ED, Cole SA, VandeBerg JL, Almasy L, Blangero J, MacCluer JW, Mahaney MC (2009) Determinants of variation in human serum paraoxonase activity. Heredity 102:147–154
Rea IM, McMaster D, Young IS, Patterson C, Savage MJ, Belton C, Marchegiani F, Olivieri F, Bonafe M, Franceschi C (2004) Paraoxonase polymorphisms PON1 192 and 55 and longevity in Italian centenarians and Irish nonagenarians: a pooled analysis. Exp Gerontol 39:629–635
Richter RJ, Furlong CE (1999) Determination of paraoxonase (PON1) status requires more than genotyping. Pharmacogenetics 9:745–753
Roest M, Jansen ACM, Barendrecht A, Leus FR, Kastelein JJP, Voorbij HAM (2005) Variation at the paraoxonase gene locus contributes to carotid arterial wall thickness in subjects with familial hypercholesterolemia. Clin Biochem 38:123–127
Roest M, van Himbergen TM, Barendrecht AB, Peeters PHM, van der Schouw YT, Voorbij HAM (2007) Genetic and environmental determinants of the PON-1 phenotype. Eur J Clin Invest 37:187–196
Rojas-García AE, Solís-Heredia MJ, Piña-Guzmán B, Vega L, López-Carrillo L, Quintanilla-Vega B (2005) Genetic polymorphisms and activity of PON1 in a Mexican population. Toxicol Appl Pharmacol 205:282–289
Rupérez AI, López-Guarnido O, Gil F, Olza J, Gil-Campos M, Leis R, Tojo R, Cañete R, Gil A, Aguilera CM (2013) Paraoxonase 1 activities and genetic variation in childhood obesity. Br J Nutr 110:1639–1647
Seres I, Paragh G, Deschene E, Fulop T Jr, Khalil A (2004) Study of factors influencing the decreased HDL associated PON1 activity with aging. Exp Gerontol 39:59–66
Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM, Lusis AJ (1998) Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 394:284–287
Shin BS (2009) Paraoxonase gene polymorphism in south-western Korean population. J Korean Med Sci 24:561–566
Sirivarasai J, Kaojarern S, Yoovathaworn K, Sura T (2007) Paraoxonase (PON1) polymorphism and activity as the determinants of sensitivity to organophosphates in human subjects. Chem Biol Interact 168:184–192
Sorenson RC, Primo-Parmo SL, Kuo C-L, Adkins S, Lockridge O, La Du BN (1995) Reconsideration of the catalytic center and mechanism of mammalian paraoxonase/arylesterase. PNAS 92:7187–7191
Srinivasan SR, Li S, Chen W, Tang R, Bond MG, Boerwinkle E, Berenson GS (2004) Q192R polymorphism of the paraoxonase 1 gene and its association with serum lipoprotein variables and carotid artery intima-media thickness in young adults from a biracial community: the Bogalusa Heart Study. Atherosclerosis 177:167–174
Sutherland WHF, Walker RJ, de Jong SA, van Rij AM, Phillips V, Walker HL (1999) Reduced postprandial serum paraoxonase activity after a meal rich in used cooking fat. Arterioscler Thromb Vasc Biol 19:1340–1347
Thyagarajan B, Jacobs DR Jr, Carr JJ, Alozie O, Steffes MW, Kailash P, Hayes JH, Gross MD (2008) Factors associated with paraoxonase genotypes and activity in a diverse, young, healthy population: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Clin Chem 54:738–746
van der Gaag MS, van Tol A, Scheek LM, James RW, Urgert R, Schaafsma G, Hendriks HFJ (1999) Daily moderate alcohol consumption increases serum paraoxonase activity; a diet-controlled, randomised intervention study in middle-aged men. Atherosclerosis 147:405–410
Wheeler JG, Keavney BD, Watkins H, Collins R, Danesh J (2004) Four paraoxonase gene polymorphisms in 11,212 cases of coronary heart disease and 12,786 controls: meta-analysis of 43 studies. Lancet 363:689–695
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This research was supported in part by National Institutes of Health ES015107. This is Center for Environmental Health Sciences publication number 129.
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McDaniel, C.Y., Dail, M.B., Wills, R.W. et al. Paraoxonase 1 Polymorphisms Within a Mississippi USA Population as Possible Biomarkers of Enzyme Activities Associated With Disease Susceptibility. Biochem Genet 52, 509–523 (2014). https://doi.org/10.1007/s10528-014-9663-8
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DOI: https://doi.org/10.1007/s10528-014-9663-8