R-carrying genotypes of serum paraoxonase (PON1) 192 polymorphism and higher activity ratio are related to susceptibility against ischemic stroke.
The polymorphic gene of serum paraoxonase (PON1) and its activity involved in atherosclerosis. The purpose of the study was to analyze PON1 192 Q/R polymorphism and the enzyme activities in ischemic stroke. The polymorphism as the most common polymorphism in PON1 gene coding sequence is associated with variation in the enzyme activity and vascular disease. The study included 85 stroke patients and 71 control subjects. PON1 192 polymorphism was genotyped using PCR protocol. Paraoxonase activity (Para) and arylesterase activity (Aryl) were determined spectrophotometrically using paraoxon and phenylacetate as the substrates. The QR and RR genotypes were more frequent in stroke population compared to controls, resulting in a higher frequency of the R allele in patients (0.24 vs 0.18, OR = 1.41). Patients had significantly higher Para/Aryl ratio than that of controls (P = 0.016). In stroke patients, Para/Aryl and Para/HDL ratios increased with this order: QQ < QR < RR. Hypertension significantly increased the risk of ischemic stroke by 15-fold among R-containing people, while this was significantly increased 4-fold for QQ homozygotes. Smoking increased the risk of having ischemic stroke in both QQ homozygote and QR + RR group (OR = 2.84 and OR = 2.33, respectively). In conclusion, these data highlight the importance of PON1 192 R allele and high Para/Aryl ratio in susceptibility to ischemic stroke in the population. The presence of the 192 R allele potentiates the risk of stroke especially in hypertensive people. Decreased Aryl and increased Para/Aryl, Para/HDL and Aryl/HDL ratios may be markers indicated the increased susceptibility to ischemic stroke in the population.
Department of Clinical Biochemistry and Genetics, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran. kmahrooz@yahoo.com
Abdolkarim
A
Mahrooz
Ghorban
G
Gohari
Mohammad-Bagher
MB
Hashemi
Mehryar
M
Zargari
Hadis
H
Musavi
Mahmoud
M
Abedini
Ahad
A
Alizadeh
D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D007511:Ischemia / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000235:genetics; D020521:Stroke / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D049629:Waist-Hip Ratio
D008075:Lipoproteins, HDL; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human