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R-carrying genotypes of serum paraoxonase (PON1) 192 polymorphism and higher activity ratio are related to susceptibility against ischemic stroke

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Abstract

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.

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Acknowledgments

This study was funded with the support of Mazandaran University of Medical Sciences, Sari, Iran.

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Authors and Affiliations

  1. Department of Clinical Biochemistry and Genetics, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Abdolkarim Mahrooz

  2. Department of Clinical Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

    Ghorban Gohari, Mohammad-Bagher Hashemi & Mehryar Zargari

  3. Department of Biochemistry, Faculty of Basic Science, Razi University, Kermanshah, Iran

    Hadis Musavi

  4. Department of Neurology, Bu Ali Teaching Hospital, Mazandaran University of Medical Sciences, Sari, Iran

    Mahmoud Abedini

  5. Department of Biostatistics, Faculty of Health, Mazandaran University of Medical Sciences, Sari, Iran

    Ahad Alizadeh

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  1. Abdolkarim Mahrooz
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  2. Ghorban Gohari
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  4. Mehryar Zargari
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Correspondence to Abdolkarim Mahrooz.

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Mahrooz, A., Gohari, G., Hashemi, MB. et al. R-carrying genotypes of serum paraoxonase (PON1) 192 polymorphism and higher activity ratio are related to susceptibility against ischemic stroke. Mol Biol Rep 39, 11177–11185 (2012). https://doi.org/10.1007/s11033-012-2027-8

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  • DOI: https://doi.org/10.1007/s11033-012-2027-8

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