S.S.-T., N.W., H.S. and E.B.A. contributed equally to this work.
Atherosclerosis and arteriosclerosis parameters in stroke patients associate with paraoxonase polymorphism and esterase activities
Article first published online: 11 JAN 2013
© 2013 The Author(s) European Journal of Neurology © 2013 EFNS
European Journal of Neurology
Volume 20, Issue 6, pages 891–898, June 2013
How to Cite
Shenhar-Tsarfaty, S., Waiskopf, N., Ofek, K., Shopin, L., Usher, S., Berliner, S., Shapira, I., Bornstein, N. M., Ritov, Y., Soreq, H. and Ben Assayag, E. (2013), Atherosclerosis and arteriosclerosis parameters in stroke patients associate with paraoxonase polymorphism and esterase activities. European Journal of Neurology, 20: 891–898. doi: 10.1111/ene.12074
- Issue published online: 12 MAY 2013
- Article first published online: 11 JAN 2013
- Manuscript Accepted: 12 NOV 2012
- Manuscript Received: 21 SEP 2012
- Israel-Science-Foundation. Grant Number: 1876/11
- white matter lesions
Background and purpose
Polymorphic paraoxonase (PON1) variants can variably prevent low- and high-density lipoprotein oxidation, but their role in provoking atherosclerosis remained unclear. We addressed this issue by profiling PON1 polymorphisms and enzymatic activities, and assessing atherosclerosis and cerebral arteriosclerosis severity in post-stroke patients.
Carotid artery intima-media-thickness (IMT), cerebral white matter lesions (WML), serum PON1 -108C/T, Q192R and L55M polymorphisms, and PON and acetylcholinesterase (AChE) enzyme activities were determined in 237 patients.
Genetic variation at the PON1 locus showed a strong influence on PON1 activity in ischaemic stroke patients, but lacked direct influence on IMT. Stroke patients with PON1 QQ192 or MM55 genotypes demonstrated lower PON and arylesterase activities at both Day 1 and 12 months post-stroke than patients with either RQ/RR192 or LM/LL55 genotypes (P < 0.001). Furthermore, patients with carotid atherosclerosis and/or cerebral arteriosclerosis expressed as IMT, carotid plaques and WML had lower 12 months PON1 activity than patients without (P = 0.02, P = 0.027 and P = 0.001, respectively), and PON and AChE hydrolysis rates were more tightly correlated in patients carrying the PON1 192R compared with the 192QQ allele, in a gene dose-dependent manner (P < 0.001).
Our findings show inverse PON1 activity–carotid atherosclerosis and –cerebral arteriosclerosis association in stroke patients: the lower the PON1 activity the more progressed is the atherosclerotic process and the weaker is the association with AChE activity. Extending previous PON1 genetic studies in stroke populations, our study emphasizes the PON1 activity as a potential anti-atherogenic element and proposes involvement of cholinesterase activities in its effects.