Analysis of paraoxonase 1 (PON1) genetic polymorphisms and activities as risk factors for ischemic stroke in Turkish population

Abstract

Paraoxonase1 (PON1) is protective against the development of atherosclerosis, a risk factor for ischemic stroke. PON1 gene has one promoter region (-107T/C) and two coding region (192Q/R and 55L/M) polymorphisms that affect the levels and catalytic efficiency of the enzyme, respectively. In this study, we aimed to determine the importance of -107T/C, 192Q/R and 55L/M polymorphisms of PON1 gene and three PON1 activities (diazoxonase, paraoxonase, arylesterase) as risk factors for ischemic stroke. Study population was comprised of 172 unrelated adult Caucasian patients with acute hemispheric ischemic stroke and 105 symptom-free controls. Genotypes were attained by PCR followed by restriction enzyme digestion and phenotypes were determined by spectrophotometric assays. This is the first study analyzing diazoxonase activity as a risk factor for ischemic stroke. Nevertheless, diazoxonase, paraoxonase and arylesterase activities were almost the same in stroke patients and controls. The -107TT genotype was associated with a 1.97 times increased risk for stroke in elderly (age > 59). Individuals with this genotype were found to have the lowest PON1 enzyme activities among the -107T/C genotypes. Triple combined haplotype QRLMTC was found to be 6.94- and 10.4-times protective against ischemic stroke in the overall and the elderly population, respectively. 55LL genotype was associated with a 1.78-fold increase in the risk of ischemic stroke. PON1 genotypes, but not activities, are related with the risk of stroke.