Paraoxonase 1: Genetics and activities during aging

Rejuvenation Research

Volumn 11, Issue 1, 2008, Pages 113-127

  Marchegiani, Francesca ^a,b   Marra, Maurizio ^a   Olivieri, Fabiola ^a   Cardelli, Maurizio ^a   James, Richard W ^c   Boemi, Massimo ^a   Franceschi, Claudio ^a,d  

^a INRCA   (Italy)

^b UNIVERSITY OF FERRARA   (Italy)

^c UNIVERSITY HOSPITAL   (Switzerland)

^d UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ARYLDIALKYLPHOSPHATASE 1; ARYLDIALKYLPHOSPHATASE 2; HIGH DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN; THROMBOCYTE ACTIVATING FACTOR;

AGING; ATHEROSCLEROSIS; GENE; GENE ACTIVITY; GENE FREQUENCY; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENETICS; GENOTYPE; HUMAN; LIPID COMPOSITION; LIPID OXIDATION; LONGEVITY; NONHUMAN; OXIDATIVE STRESS; PON1 GENE; PRIORITY JOURNAL; PROTEIN PROCESSING; REVIEW;

AGING; ANIMALS; ARYLDIALKYLPHOSPHATASE; ATHEROSCLEROSIS; HUMANS; VARIATION (GENETICS);

EID: 39449136466     PISSN: 15491684     EISSN: None     Source Type: Journal    
DOI: 10.1089/rej.2007.0582     Document Type: Review

References (117)

1. Martin GM, Austad SN, Johnson TE. Genetic analysis of ageing: role of oxidative damage and environmental stresses. Nat Genet 1996;13:25-34.
2. Evert J, Lawler E, Bogan H, Perls T. Morbidity profiles of centenarians: survivors, delayers, and escapers. J Gerontol A Biol Sci Med Sci 2003;58:232-237.
3. Franceschi C, Bonafe M. Centenarians as a model for healthy aging. Biochem Soc Trans 2003;31:457-461.
4. Perls T, Terry D. Understanding the determinants of exceptional longevity. Ann Intern Med 2003;139:445-449.
5. Perls T. The different paths to age one hundred. Ann NY Acad Sci 2005;1055:13-25.
6. Franceschi C, Olivieri F, Marchegiani F, Cardelli M, Cavallone L, Capri M, Salvioli S, Valensin S, De Benedictis G, Di Iorio A, Caruso C, Paolisso G, Monti D. Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians. Mech Ageing Dev 2005;126:351-361.
7. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol 1956;11:298-300.
8. Chait A, Han CY, Oram JF, Heinecke JW. Thematic review series: the immune system and atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease? J Lipid Res 2005;46:389-403.
9. Baggio G, Donazzan S, Monti D, Mari D, Martini S, Gabelli C, Dalla Vestra M, Previato L, Guido M, Pigozzo S, Cortella I, Crepaldi G, Franceschi C. Lipoprotein(a) and lipoprotein profile in healthy centenarians: a reappraisal of vascular risk factors. FASEB J 1998;12:433-437.
10. Harel M, Aharoni A, Gaidukov L, Brumshtein B, Khersonsky O, Meged R, Dvir H, Ravelli RB, McCarthy A, Toker L, Silman I, Sussman JL, Tawfik DS. Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 2004;11:412-419.
11. James RW, Deakin SP. The importance of high-density lipoproteins for paraoxonase-1 secretion, stability, and activity. Free Rad Biol Med 2004;37:1986-1994.
12. Sorenson RC, Bisgaier CL, Aviram M, Hsu C, Billecke S, La Du BN. Human serum paraoxonase/arylesterase's retained hydrophobic N-terminal leader sequence associates with HDLs by binding phospholipids: apolipoprotein A-I stabilizes activity. Arterioscler Thromb Vasc Biol 1999;19:2214-2225.
13. Navab M, Hama-Levy S, Van Lenten BJ, Fonarow GC, Cardinez CJ, Castellani LW, Brennan ML, Lusis AJ, Fogelman AM, La Du BN. Mildly oxidized LDL induces an increased apolipoprotein J/paraoxonase ratio. J Clin Invest 1997;99:2005-2019.
14. Aviram M, Billecke S, Sorenson R, Bisgaier C, Newton R, Rosenblat M, Erogul J, Hsu C, Dunlop C, La Du B. 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 1998;18:1617-1624.
15. 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;101:1581-1590.
16. Aviram M. Does paraoxonase play a role in susceptibility to cardiovascular disease? Mol Med Today 1999;5:381-386.
17. Aviram M, Rosenblat M, Billecke S, Erogul J, Sorenson R, Bisgaier CL, Newton RS, La Du B. Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med 1999;26:892-904.
18. Mackness MI, Mackness B, Durrington PN, Connelly PW, Hegele RA. Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins. Curr Opin Lipidol 1996;7:69-76.
19. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, Navab M. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 1995;96:2882-2891.
20. Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, Hayek T, Presser D, Fuhrman B. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr 2000;71:1062-1076.
21. Aviram M, Hardak E, Vaya J, Mahmood S, Milo S, Hoffman A, Billicke S, Draganov D, Rosenblat M. 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 2000;101:2510-2517.
22. Mackness MI, Arrol S, Durrington PN. Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett 1991;292:307.
23. Mertens A, Holvoet P. Oxidized LDL and HDL: antagonists in atherothrombosis. FASEB J 2001;15:2073-2084.
24. Navab M, Hama SY, Hough GP, Hedrick CC, Sorenson R, La Du BN, Kobashigawa JA, Fonarow GC, Berliner JA, Laks H, Fogelman AM. High density associated enzymes: their role in vascular biology. Curr Opin Lipidol 1998;9:449-456.
25. Azizi F, Raiszadeh F, Solati M, Etemadi A, Rahmani M, Arabi M. Serum paraoxonase 1 activity is decreased in thyroid dysfunction. J Endocrinol Invest 2003;26:703-709.
26. Senti M, Tomas M, Fito M, Weinbrenner T, Covas MI, Sala J, Masia R, Marrugat J. Antioxidant paraoxonase 1 activity in the metabolic syndrome. J Clin Endocrinol Metab 2003;88:5422-5426.
27. Biasioli S, Schiavon R, Petrosino L, De Fanti E, Cavalcanti G, Battaglia P, Fasolin A. Paraoxonase activity and paraoxonase 1 gene polymorphism in patients with uremia. ASAIO J 2003;49:295-299.
28. Tanimoto N, Kumon Y, Suehiro T, Ohkubo S, Ikeda Y, Nishiya K, Hashimoto K. Serum paraoxonase activity decreases in rheumatoid arthritis. Life Sci 2003;72:2877-2885.
29. MacKness B, Mackness MI, Durrington PN, Arrol S, Evans AE, McMaster D, Ferrieres J, Ruidavets JB, Williams NR, Howard AN. Paraoxonase activity in two healthy populations with differing rates of coronary heart disease. Eur J Clin Invest 2000;30:4-10.
30. Mackness B, Durrington PN, Boulton AJ, Hine D, Mackness MI. Serum paraoxonase activity in patients with type 1 diabetes compared to healthy controls. Eur J Clin Invest 2002;32:259-264.
31. Dantoine TF, Debord J, Charmes JP, Merle L, Marquet P, Lachatre G, Leroux-Robert C. Decrease of serum paraoxonase activity in chronic renal failure. J Am Soc Nephrol 1998;9:2082-2088.
32. Paragh G, Seres I, Balogh Z, Varga Z, Karpati I, Matyus J, Ujhelyi L, Kakuk G. The serum paraoxonase activity in patients with chronic renal failure and hyperlipidemia. Nephron 1998;80:166-170.
33. Abbott CA, Mackness MI, Kumar S, Boulton AJ, Durrington PN. Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. Arterioscler Thromb Vasc Biol 1995;15:1812-1818.
34. Mackness MI, Durrington PN. Paraoxonase: another factor in NIDDM cardiovascular disease. Lancet 1995;346:856.
35. Mackness B, Mackness MI, Arrol S, Turkie W, Julier K, Abuasha B, Miller JE, Boulton AJ, Durrington PN. Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus. Atherosclerosis 1998;139:341-349.
36. Reddy ST, Wadleigh DJ, Grijalva V, Ng C, Hama S, Gangopadhyay A, Shih DM, Lusis AJ, Navab M, Fogelman AM. Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler Thromb Vasc Biol 2001;21:542-547.
37. Mackness MI, Arrol S, Abbott C, Durrington PN. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis 1993;104:129-135.
38. Sorenson RC, Primo-Parmo SL, Kuo CL, Adkins S, Lockridge O, La Du BN. Reconsideration of the catalytic center and mechanism of mammalian paraoxonase/arylesterase. Proc Natl Acad Sci USA 1995;92:7187-7191.
39. Rosenblat M, Gaidukov L, Khersonsky O, Vaya J, Oren R, Tawfik DS, Aviram M. The catalytic histidine dyad of high density lipoprotein-associated serum paraoxonase-1 (PON1) is essential for PON1-mediated inhibition of low density lipoprotein oxidation and stimulation of macrophage cholesterol efflux. J Biol Chem 2006;281:7657-7665.
40. Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM, Lusis AJ. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 1998;394:284-287.
41. Oda MN, Bielicki JK, Ho TT, Berger T, Rubin EM, Forte TM. Paraoxonase 1 overexpression in mice and its effect on high-density lipoproteins. Biochem Biophys Res Commun 2002;290:921-927.
42. Tward A, Xia YR, Wang XP, Shi YS, Park C, Castellani LW, Lusis AJ, Shih DM. Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation 2002;106:484-490.
43. Shih DM, Xia YR, Wang XP, Miller E, Castellani LW, Subbanagounder G, Cheroutre H, Faull KF, Berliner JA, Witztum JL, Lusis AJ. Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem 2000;275:17527-17535.
44. Rozenberg O, Rosenblat M, Coleman R, Shih DM, Aviram M. Paraoxonase (PON1) deficiency is associated with increased macrophage oxidative stress: studies in PON1-knockout mice. Free Rad Biol Med 2003;34:774-784.
45. Barter PJ, Nicholls S, Rye KA, Anantharamaiah GM, Navab M, Fogelman AM. Antiinflammatory properties of HDL. Circ Res 2004;95:764-772.
46. Navab M, Berliner JA, Watson AD, Hama SY, Territo MC, Lusis AJ, Shih DM, Van Lenten BJ, Frank JS, Demer LL, Edwards PA, Fogelman AM. The Yin and Yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol 1996;16:831-842.
47. Khersonsky O, Tawfik DS. Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase. Biochemistry 2005;44:6 371-6382.
48. Adams TB, Greer DB, Doull J, Munro IC, Newberne P, Portoghese PS, Smith RL, Wagner BM, Weil CS, Woods LA, Ford RA. The FEMA GRAS assessment of lactones used as a flavour ingredients. The Flavor and Extract Manufacturers' Association. Generally recognized as safe. Food Chem Toxicol 1998;36:249-278.
49. Billecke S, Draganov D, Counsell R, Stetson P, Watson C, Hsu C, La Du BN. Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos 2000;28:1335-1342.
50. Gaidukov L, Tawfik DS. High affinity, stability, and lactonase activity of serum paraoxonase PON1 anchored on HDL with ApoA-I. Biochemistry 2005;44:11843-11854.
51. Teiber JF, Draganov DI, La Du BN. Lactonase and lactonizing activities of human serum paraoxonase (PON1) and rabbit serum PON3. Biochem Pharmacol 2003;66:887-896.
52. Rodrigo L, Mackness B, Durrington PN, Hernandez A, Mackness MI. Hydrolysis of platelet-activating factor by human serum paraoxonase. Biochem J 2001;354:1-7.
53. Ahmed Z, Ravandi A, Maguire GF, Emili A, Draganov D, La Du BN, Kuksis A, Connelly PW. Multiple substrates for paraoxonase-1 during oxidation of phosphatidylcholine by peroxynitrite. Biochem Biophys Res Commun 2002;290:391-396.
54. Jakubowski H. Protein homocysteinylation: possible mechanism underlying pathological consequences of elevated homocysteine levels. FASEB J 1999;13:2277-2283.
55. Jakubowski H, Zhang L, Bardeguez A, Aviv A. Homocysteine thiolactone and protein homocysteinylation in human endothelial cells: implications for atherosclerosis. Circ Res 2000;87:45-51.
56. Jakubowski H. Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J Biol Chem 2000;275:3957-3962.
57. Jakubowski H, Ambrosius WT, Pratt JH. Genetic determinants of homocysteine thiolactonase activity in humans: implications for atherosclerosis. FEBS Lett 2001;491:35-39.
58. Jakubowski H. Translational accuracy of aminoacyl-tRNA synthetases: implications for atherosclerosis. J Nutr 2001;131:2983S-2987S.
59. Ferretti G, Bacchetti T, Marotti E, Curatola G. Effect of homocysteinylation on human high-density lipoproteins: a correlation with paraoxonase activity. Metabolism 2003;52:146-151.
60. 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;52:598-608.
61. 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;3:73-76.
62. Garin MC, James RW, Dussoix P, Blanche H, Passa P, Froguel P, Ruiz J. 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 1997;99:62-66.
63. Iselius L, Evans DA, Playfer JR. Genetics of plasma paroxonase activity. J Med Genet 1982;19:424-426.
64. Leviev I, James RW. Promoter polymorphisms of human paraoxonase PON1 gene and serum paraoxonase activities and concentrations. Arterioscler Thromb Vasc Biol 2000;20:516-521.
65. Brophy VH, Jampsa RL, Clendenning JB, McKinstry LA, Jarvik GP, Furlong CE. Effects of 5-′ regulatory-region polymorphisms on paraoxonasegene (PON1) expression. Am J Hum Genet 2001;68:1428-1436.
66. Deakin S, Leviev I, Brulhart-Meynet MC, James RW. Paraoxonase-1 promoter haplotypes and serum paraoxonase: a predominant role for polymorphic position-107, implicating the Sp1 transcription factor. Biochem J 2003;372:643-649.
67. Davies HG, Richter RJ, Keifer M, Broomfield CA, Sowalla J, Furlong CE. The effect of the human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin. Nat Genet 1996;14:334-336.
68. James RW, Leviev I, Righetti A. Smoking is associated with reduced serum paraoxonase activity and concentration in patients with coronary artery disease. Circulation 2000;101:2252-2257.
69. Senti M, Tomas M, Anglada R, Elosua R, Marrugat J, Covas MI, Fito M. Interrelationship of smoking, paraoxonase activity, and leisure time physical activity: a population-based study. Eur J Intern Med 2003;14:178-184.
70. Ferre N, Camps J, Fernandez-Ballart J, Arija V, Murphy MM, Ceruelo S, Biarnes E, Vilella E, Tous M, Joven J. Regulation of serum paraoxonase activity by genetic, nutritional, and lifestyle factors in the general population. Clin Chem 2003;49:1491-1497.
71. Van der Gaag MS, van Tol A, Scheek LM, James RW, Urgert R, Schaafsma G, Hendriks HF. Daily moderate alcohol consumption increases serum paraoxonase activity; a diet-controlled, randomised intervention study in middle-aged men. Atherosclerosis 1999;147:405-410.
72. Sierksma A, van der Gaag MS, van Tol A, James RW, Hendriks HF. Kinetics of HDL cholesterol and paraoxonase activity in moderate alcohol consumers. Alcohol Clin Exp Res 2002;26:1430-1435.
73. Tomas M, Senti M, Garcia-Faria F, Vila J, Torrents A, Covas M, Marrugat J. Effect of simvastatin therapy on paraoxonase activity and related lipoproteins in familial hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 2000;20:2113-2119.
74. Sutherland WH, Manning PJ, de Jong SA, Allum AR, Jones SD, Williams SM. Hormone-replacement therapy increases serum paraoxonase arylesterase activity in diabetic postmenopausal women. Metabolism 2001;50:319-324.
75. Beer S, Moren X, Ruiz J, James RW. Postprandial modulation of serum paraoxonase activity and concentration in diabetic and non-diabetic subjects. Nutr Metab Cardiovasc Dis 2006;16:457-465.
76. Thomas-Moya E, Nadal-Casellas A, Gianotti M, Llado I, Proenza AM. Time-dependent modulation of rat serum paraoxonase 1 activity by fasting. Pflugers Arch 2007;453:831-837.
77. Ferretti G, Bacchetti T, Moroni C, Savino S, Liuzzi A, Balzola F, Bicchiega V. Paraoxonase activity in high-density lipoproteins: a comparison between healthy and obese females. J Clin Endocrinol Metab 2005;90:1728-1733.
78. Cherki M, Derouiche A, Drissi A, El Messal M, Bamou Y, Idrissi-Ouadghiri A, Khalil A, Adlouni A. Consumption of argan oil may have an antiatherogenic effect by improving paraoxonase activities and antioxidant status: intervention study in healthy men. Nutr Metab Cardiovasc Dis 2005;15:352-360.
79. Tomas M, Senti M, Elosua R, Vila J, Sala J, Masia R, Marrugat J. Interaction between the Gln-Arg 192 variants of the paraoxonase gene and oleic acid intake as a determinant of high-density lipoprotein cholesterol and paraoxonase activity. Eur J Pharmacol 2001;432:121-128.
80. Wallace AJ, Sutherland WH, Mann JI, Williams SM. The effect of meals rich in thermally stressed olive and safflower oils on postprandial serum paraoxonase activity in patients with diabetes. Eur J Clin Nutr 2001;55:951-958.
81. Jarvik GP, Tsai NT, McKinstry LA, Wani R, Brophy VH, Richter RJ, Schellenberg GD, Heagerty PJ, Hatsukami TS, Furlong CE. Vitamin C and E intake is associated with increased paraoxonase activity. Arterioscler Thromb Vasc Biol 2002;22:1329-1333.
82. Kleemola P, Freese R, Jauhiainen M, Pahlman R, Alfthan G, Mutanen M. Dietary determinants of serum paraoxonase activity in healthy humans. Atherosclerosis 2002;160:425-432.
83. Hu Y, Tian H, Liu R. Gln-Arg192 polymorphism of paraoxonase 1 is associated with carotid intima-media thickness in patients of type 2 diabetes mellitus of Chinese. Diabetes Res Clin Pract 2003;61:21-27.
84. Chen Q, Reis SE, Kammerer CM, McNamara DM, Holubkov R, Sharaf BL, Sopko G, Pauly DF, Merz CN, Kamboh MI. Association between the severity of angiographic coronary artery disease and paraoxonase gene polymorphisms in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. Am J Hum Genet 2003;72:13-22.
85. Voetsch B, Benke KS, Damasceno BP, Siqueira LH, Loscalzo J. Paraoxonase 192 Gln->Arg polymorphism: an independent risk factor for nonfatal arterial ischemic stroke among young adults. Stroke 2002;33:1459-1464.
86. Imai Y, Morita H, Kurihara H, Sugiyama T, Kato N, Ebihara A, Hamada C, Kurihara Y, Shindo T, Ohhashi Y, Yazaki Y. Evidence for association between paraoxonase gene polymorphisms and atherosclerotic diseases. Atherosclerosis 2000;149:435-442.
87. Pfohl M, Koch M, Enderle MD, Kuhn R, Fullhase J, Karsch KR, Haring HU. Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes. Diabetes 1999;48:623-627.
88. Kondo I, Yamamoto M. Genetic polymorphism of paraoxonase 1 (PON1) and susceptibility to Parkinson's disease. Brain Res 1998;806:271-273.
89. 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;15:89-95.
90. Odawara M, Tachi Y, Yamashita K. Paraoxonase polymorphism (Gln192-Arg) is associated with coronary heart disease in Japanese noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1997;82:2257-2260.
91. Marra M, Marchegiani F, Antonicelli R, Sirolla C, Spazzafumo L, Olivieri F, Franceschi C, Testa R, Paolisso G, James RW, Boemi M, Parati G. The PON1192RR genotype is associated with a higher prevalence of arterial hypertension. J Hypertens 2006;24:1293-1298.
92. Lawlor DA, Day IN, Gaunt TR, Hinks LJ, Briggs PJ, Kiessling M, Timpson N, Smith GD, Ebrahim S. The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a metaanalysis. BMC Genet 2004;5:17.
93. Schmidt H, Schmidt R, Niederkorn K, Gradert A, Schumacher M, Watzinger N, Hartung HP, Kostner GM. Paraoxonase PON1 polymorphism leu-Met54 is associated with carotid atherosclerosis: results of the Austrian Stroke Prevention Study. Stroke 1998;29:2043-2048.
94. Leviev I, Negro F, James RW. 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;17:2935-2939.
95. Mackness B, Mackness MI, Arrol S, Turkie W, Durrington PN. Effect of the molecular polymorphisms of human paraoxonase (PON1) on the rate of hydrolysis of paraoxon. Br J Pharmacol 1997;122:265-268.
96. Akhmedova SN, Yakimovsky AK, Schwartz EI. Paraoxonase 1 Met - Leu 54 polymorphism is associated with Parkinson's disease. J Neurol Sci 2001;184:179-182.
97. Malin R, Jarvinen O, Sisto T, Koivula T, Lehtimaki T. Paraoxonase producing PON1 gene M/L55 polymorphism is related to autopsy-verified artery-wall atherosclerosis. Atherosclerosis 2001;157:301-307.
98. Malin R, Loimaala A, Nenonen A, Mercuri M, Vuori I, Pasanen M, Oja P, Bond G, Koivula T, Lehtimaki T. Relationship between high-density lipoprotein paraoxonase gene M/L55 polymorphism and carotid atherosclerosis differs in smoking and nonsmoking men. Metabolism 2001;50:1095-1101.
99. Fortunato G, Rubba P, Panico S, Trono D, Tinto N, Mazzaccara C, De Michele M, Iannuzzi A, Vitale DF, Salvatore F, Sacchetti L. A paraoxonase gene polymorphism, PON 1 (55), as an independent risk factor for increased carotid intima-media thickness in middle-aged women. Atherosclerosis 2003;167:141-148.
100. 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;42:528-535.
101. 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;363:689-695.
102. Bonafe M, Marchegiani F, Cardelli M, Olivieri F, Cavallone L, Giovagnetti S, Pieri C, Marra M, Antonicelli R, Troiano L, Gueresi P, Passeri G, Berardelli M, Paolisso G, Barbieri M, Tesei S, Lisa R, De Benedictis G, Franceschi C. Genetic analysis of Paraoxonase (PON1) locus reveals an increased frequency of Arg192 allele in centenarians. Eur J Hum Genet 2002;10:292-296.
103. Rea IM, McKeown PP, McMaster D, Young IS, Patterson C, Savage MJ, Belton C, Marchegiani F, Olivieri F, Bonafe M, Franceschi C. Paraoxonase polymorphisms PON1 192 and 55 and longevity in Italian centenarians and Irish nonagenarians. A pooled analysis. Exp Gerontol 2004;39:629-635.
104. Christiansen L, Bathum L, Frederiksen H, Christensen K. Paraoxonase 1 polymorphisms and survival. Eur J Hum Genet 2004;12:843-847.
105. Tan Q, Christiansen L, Christensen K, Bathum L, Li S, Zhao JH, Kruse TA. Haplotype association analysis of human disease traits using genotype data of unrelated individuals. Genet Res 2005;86:223-231.
106. Tan Q, Christiansen L, Bathum L, Li S, Kruse TA, Christensen K. Genetic association analysis of human longevity in cohort studies of elderly subjects: an example of the PON1 gene in the Danish 1905 birth cohort. Genetics 2006;172:1821-1828.
107. Heijmans BT, Westendorp RG, Lagaay AM, Knook DL, Kluft C, Slagboom PE. Common paraoxonase gene variants, mortality risk and fatal cardiovascular events in elderly subjects. Atherosclerosis 2000;149:91-97.
108. Marchegiani F, Marra M, Spazzafumo L, James RW, Boemi M, Olivieri F, Cardelli M, Cavallone L, Bonfigli AR, Franceschi C. Paraoxonase activity and genotype predispose to successful aging. J Gerontol A Biol Sci Med Sci 2006;61:541-546.
109. Bonafe M, Olivieri F, Cavallone L, Giovagnetti S, Marchegiani F, Cardelli M, Pieri C, Marra M, Antonicelli R, Lisa R, Rizzo MR, Paolisso G, Monti D, Franceschi C. A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol 2001;31:2357-2361.
110. Olivieri F, Bonafe M, Cavallone L, Giovagnetti S, Marchegiani F, Cardelli M, Mugianesi E, Giampieri C, Moresi R, Stecconi R, Lisa R, Franceschi C. The -174 C/G locus affects in vitro/in vivo IL-6 production during aging. Exp Gerontol 2002;37:309-314.
111. Cabana VG, Reardon CA, Feng N, Neath S, Lukens J, Getz GS. Serum paraoxonase: effect of the apolipoprotein composition of HDL and the acute phase response. J Lipid Res 2003;44:780-792.
112. Feingold KR, Memon RA, Moser AH, Grunfeld C. Paraoxonase activity in the serum and hepatic mRNA levels decrease during the acute phase response. Atherosclerosis 1998;139:307-315.
113. Kumon Y, Nakauchi Y, Kidawara K, Fukushima M, Kobayashi S, Ikeda Y, Suehiro T, Hashimoto K, Sipe JD. A longitudinal analysis of alteration in lecithin-cholesterol acyltransferase and paraoxonase activities following laparoscopic cholecystectomy relative to other parameters of HDL function and the acute phase response. Scand J Immunol 1998;48:419-424.
114. Van Lenten BJ, Wagner AC, Nayak DP, Hama S, Navab M, Fogelman AM. High-density lipoprotein loses its anti-inflammatory properties during acute influenza a infection. Circulation 2001;103:2283-2288.
115. Seres I, Paragh G, Deschene E, Fulop T, Khalil A. Study of factors influencing the decreased HDL associated PON1 activity with aging. Exp Gerontol 2004;39:59-66.
116. Jaouad L, de Guise C, Berrougui H, Cloutier M, Isabelle M, Fulop T, Payette H, Khalil A. Age-related decrease in high-density lipoproteins antioxidant activity is due to an alteration in the PON1's free sulfhydryl groups. Atherosclerosis 2006;185:191-200.
117. Campo S, Sardo MA, Trimarchi G, Bonaiuto M, Fontana L, Castaldo M, Bonaiuto A, Saitta C, Bitto A, Manduca B, Riggio S, Saitta A. Association between serum paraoxonase (PON1) gene promoter T(-107)C polymorphism, PON1 activity and HDL levels in healthy Sicilian octogenarians. Exp Gerontol 2004;39:1089-1094.