Atherosclerosis and arteriosclerosis parameters in stroke patients associate with paraoxonase polymorphism and esterase activities.

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Title: Atherosclerosis and arteriosclerosis parameters in stroke patients associate with paraoxonase polymorphism and esterase activities.
Authors: Shenhar‐Tsarfaty, S., Waiskopf, N., Ofek, K., Shopin, L., Usher, S., Berliner, S., Shapira, I., Bornstein, N. M., Ritov, Y., Soreq, H., Ben Assayag, E.
Source: European Journal of Neurology. Jun2013, Vol. 20 Issue 6, p891-898. 8p. 1 Diagram, 3 Graphs.
Subjects: Paraoxonase, Lipoproteins, Genetic polymorphisms, Cerebral arteriosclerosis, Human genetic variation, Cerebrovascular disease patients, Cholinesterases
Abstract: 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. Methods Carotid artery intima-media-thickness ( IMT), cerebral white matter lesions ( WML), serum PON1 -108 C/ T, Q192 R and L55 M polymorphisms, and PON and acetylcholinesterase (AChE) enzyme activities were determined in 237 patients. Results 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 192 R compared with the 192 QQ allele, in a gene dose-dependent manner ( P < 0.001). Conclusion 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. [ABSTRACT FROM AUTHOR]
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Database: Psychology and Behavioral Sciences Collection
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Abstract: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. Methods Carotid artery intima-media-thickness ( IMT), cerebral white matter lesions ( WML), serum PON1 -108 C/ T, Q192 R and L55 M polymorphisms, and PON and acetylcholinesterase (AChE) enzyme activities were determined in 237 patients. Results 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 192 R compared with the 192 QQ allele, in a gene dose-dependent manner ( P < 0.001). Conclusion 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. [ABSTRACT FROM AUTHOR]
ISSN:13515101
DOI:10.1111/ene.12074