title: Atherosclerosis and arteriosclerosis parameters in stroke patients associate with paraoxonase polymorphism and esterase activities.
abstract: OBJECTIVE
  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 -108C/T, Q192R and L55M 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 192R compared with the 192QQ allele, in a gene dose-dependent manner (P < 0.001).
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Institute of Life Sciences and the Edmond and Lily Safra Center of Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Shenhar-Tsarfaty
authors.forename: N
authors.initials: N
authors.lastname: Waiskopf
authors.forename: K
authors.initials: K
authors.lastname: Ofek
authors.forename: L
authors.initials: L
authors.lastname: Shopin
authors.forename: S
authors.initials: S
authors.lastname: Usher
authors.forename: S
authors.initials: S
authors.lastname: Berliner
authors.forename: I
authors.initials: I
authors.lastname: Shapira
authors.forename: N M
authors.initials: NM
authors.lastname: Bornstein
authors.forename: Y
authors.initials: Y
authors.lastname: Ritov
authors.forename: H
authors.initials: H
authors.lastname: Soreq
authors.forename: E
authors.initials: E
authors.lastname: Ben Assayag
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020521:Stroke / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*
chemical_list: D000110:Acetylcholinesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human