Abstract
The gene of an esterase enzyme, called paraoxonase (PON, EC.3.1.8.1.) is a member of a multigene family that comprises three related genes PON1, PON2, and PON3 with structural homology clustering on the chromosome 7.1,2 The PON1 activity and the polymorphism of the PON1 and PON2 genes have been found to be associated with risk of cardiovascular diseases such as hypercholesterolaemia, non-insulin-dependent diabetes, coronary heart disease (CHD) and myocardial infaction.3–8 The importance of cardiovascular risk factors in the pathomechanism of Alzheimer's disease (AD) and vascular dementia (VD)9–13 prompted us to examine the genetic effect of PON2 gene codon 311 (Cys→Ser; PON2*S) polymorphism and the relationship between the PON2*S allele and the other dementia risk factor, the apoE polymorphism in these dementias. The PON2*C and PON2*S allele frequencies were similar in both AD (25% and 75%) and VD groups (23% and 77%), respectively, compared with the controls (27% and 73%). The ratio of the PON2*S carriers was significantly higher among the apoE4 allele carrier AD (27%) and VD (25%) groups than in the control (12%). Our results indicate that the PON2*S and apoE4 alleles have interactive effect on the development of the two most common forms of dementias AD and VD, and further support the hypothesis that cardiovascular factors contribute to the development of AD.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Sorenson RC, Primo-Parmo SL, Camper SA, La Du BN . The genetic mapping and gene structure of mouse paraoxonase/arylesterase Genomics 1995 30: 431–438
Primo-Parmo SL, Sorenson RC, Teiber J, La Du BN . The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family Genomics 1996 382: 498–507
McElween J, Mackness MI, Colley CM, Perad T, Warner S, Walker CH . Distribution of paraoxonase hydrolytic activity in the serum of patients after myocardial infarction Clin Chem 1986 32: 671–673
Mackness MI, Harty D, Bhatnagar D, Winocur PH, Arrol S, Ishola M et al. Serum paraoxonase activity in familial hypercholesterolaemia and insulin-dependent diabetes mellitus Atherosclerosis 1991 86: 193–199
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
Ruiz J, Blanche H, James RW, Garin MC, Vaisse C, Charpentier G et al. Gln-Arg192 polymorphism of paraoxonase and coronary heart disease in type 2 diabetes Lancet 1995 346: 869–872
Garin MC, James RW, Dussoix P, Blanche H, Passa P, Froguel P et al. Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes J Clin Invest 1997 99: 62–66
Rice GI, Ossei-Gerning N, Stickland MH, Grant PJ . The paraoxonase Gln-Arg 192 polymorphism in subjects with ischaemic heart disease Coronary Artery Disease 1997 8: 677–682
De la Torre JC . Critical threshold cerebral hypoperfusion causes Alzheimer's disease? Acta Neuropathologica 1999 98: 1–8
Sparks DL . Intraneuronal β-amyloid immunoreactivity in the CNS Neurobiol Aging 1995 17: 291–299
Guo Z, Viitanen M, Fratiglioni L, Winblad B . Low blood pressure and dementia in elderly people: the Kungsholmen project Br Med J 1996 312: 805–808
Kálmán J, Juhász A, Császár A, Kanka A, Maglóczky E, Bencsik K et al. Apolipoprotein E allele frequencies in patients with late onset sporadic Alzheimer's dementia in Hungary Acta Neurol Scand 1997 95: 56–59
Kálmán J, Juhász A, Császár A, Kanka A, Rimanóczy Á, Janka Z et al. Increased apolipoprotein frequency is associated with vascular dementia in the Hungarian population Acta Neurol Scand 1998 98: 166–168
Sanghera DK, Aston CE, Saha N, Kamboh MI . DNA polymorphism in two paraoxonase genes (PON1 and PON2) are associated with the risk of coronary heart disease Am J Hum Genet 1998 62: 36–44
Antakainen M, Murtomaki S, Syvanne M, Pahlman R, Tahvanainen E, Jauhiainen M et al. The Gln-Arg 192 polymorphism of the human paraoxonase gene (HUMPONA) is not associated with the risk of the coronary artery disease in Finns J Clin Invest 1996 98: 883–885
Ombres D, Pannitteri G, Montali A, Candeloro A, Seccareccia F, Campagna F et al. The Gln-Arg 192 polymorphism of human paraoxonase gene is not associated with coronary artery disease in Italian patients Arterioscler Thromb Vasc Biol 1998 18: 1611–1616
Harding RM, Sokal RR . Classification of the European language families by genetic distance Proc Natl Acad Sci USA 1988 85: 9370–9372
Hallman DM, Boerwinkle E, Saha N, Sandholzer C, Menzel HJ, Császár A et al. The apolipoprotein E polymorphism: a comparison of allele frequencies and effects in nine populations Am J Hum Genet 1991 49: 338–349
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
Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM et al. Protective effect of high density lipoprotein associated paraoxonase J Clin Invest 1995 96: 2882–2891
Mackness B, Mackness MI, Arrol S, Turkie W, Julier K, Abuasha B et al. Serum paraoxonase (PON1) 55 and 192 polymorphism and paraoxonase activity and concentration in non-insulin dependent diabetes mellitus Atherosclerosis 1998 139: 341–349
Kálmán J, Kudchodkar BJ, Murray K, McConathy WJ, Juhász A, Janka Z et al. Evaluation of serum-lipid related cardiovascular risk factors in Alzheimer's disease Dementia Geriatr Cogn Dis 1999 10: 488–493
Sodeyama N, Yamada M, Itoh Y, Suematsu N, Matsushita M, Otomo E . No association of paraoxonase gene polymorphism with atherosclerosis or Alzheimer's disease Neurology 1999 53: 1146–1148
Császár A, Kálmán J, Szalai Cs, Janka Z, Romics L . Association of the apolipoprotein A-IV codon 360 mutation in patients with Alzheimer's disease Neurosci Lett 1997 230: 1–4
Miller SA, Dykes DD, Polesky HF . A simple salting out procedure for extracting DNA from human nucleated cells Nucl Acid Res 1988 16: 1215–1218
Acknowledgements
The authors wish to thank all the probands who participated in the study. This work has been supported by a grant from the Health Scientific Board ETT 01817/2000, Hungary.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Janka, Z., Juhász, A., Rimanóczy, Á. et al. Codon 311 (Cys → Ser) polymorphism of paraoxonase-2 gene is associated with apolipoprotein E4 allele in both Alzheimer's and vascular dementias. Mol Psychiatry 7, 110–112 (2002). https://doi.org/10.1038/sj.mp.4000916
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.mp.4000916