Date

2014

Author

Bilgin, Esra

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Stroke is defined as the acute neurological cerebrovascular disease based on interruptions to blood flow in the brain. These interruptions are caused by loss of blood supply due to vessel bursts or vessel blocked by clotting. Atherosclerosis, a main cause of stroke, is blockage of endothelium layer of arteries and losing the flexibility of tissue. The oxidative stress is known as a risk factor for atherosclerosis. The increased free radicals such as reactive oxygen species (ROS) and decreased antioxidant level cause the oxidative stress and this situation damages the tissue on brain and blood vessels. Oxidative stress is influenced by imbalance in production of phase II enzymes which are responsible for xenobiotic mechanism in terms of decreasing oxidative stress. Glutathione S-transferase omega 1 and omega 2 are members of phase II enzymes family which catalyze detoxification reactions. The polymorphisms, Ala140Asp (C→A) in GSTO1 gene and Asn142Asp (A→G) in GSTO2 gene may cause a decrease in enzyme activity and this situation promotes oxidative stress damage in blood vessels. The aim of this study is to investigate the possible association between GSTO1 Ala140Asp and GSTO2 Asn142Asp SNPs and ischemic stroke risk in Turkish population. The study population includes 239 patients and 130 controls and both polymorphisms were determined by PCR/RFLP method. Conventional risk factors for ischemic stroke such as hypertension, diabetes mellitus, obesity and smoking were found significantly higher in patients compared to controls (Odds Ratios; OR=3.35, OR=2.614, OR=4.191 and OR=2.662, respectively). Mutant allele ‘A’ frequencies for Ala140Asp polymorphism of GSTO1 gene were calculated as 0.358 for patients and 0.342 for controls. For the Asn142Asp SNP of GSTO2 gene, the mutant allele ‘G’ frequencies were found 0.370 for patients and 0.404 for controls. There was no statistically significant difference between patients and controls in terms of allele frequencies. Detailed analyses have shown that stroke risk can change depending on the genotypes of GSTO1 and GSTO2 genes within conventional risk factors. For Ala140Asp SNP, the risk of having stroke is significantly lower within hypertensive subgroup and obesity subgroup when the individual carrying the mutant allele (OR=2.24 for hypertensive and OR=2.75 for obesity subgroup). Besides, having mutant allele increased the stroke risk for diabetics and smokers (OR=3.873 for diabetics and OR=3.55 for smokers). As regard to Asn142Asp SNP, the mutant allele caused an increase in stroke risk for people with obesity while decrease in diabetics (OR=9.09 for obesity and OR=2.4 for diabetics). In addition, the wild type allele increased the stroke risk for smokers (OR=3.171). Logistic regression analysis revealed that hypertension, smoking, obesity and HDL were significant predictors of stroke. Hypertension, smoking and obesity increased the stroke risk (OR= 3.043, OR=3.258 and OR=2.593, respectively) while HDL had protective role (OR=0.270). In this study, the association between Ala140Asp of GSTO1 and Asn142Asp of GSTO2 genetic polymorphisms and ischemic stroke risk in Turkish population was investigated for the first time. No significant difference was found between patient and control groups in terms of C and A allele frequencies in GSTO1 Ala140Asp polymorphism and A and G allele frequencies in GSTO2 Asn142Asp polymorphism. However, different genotypes of GSTO1 and GSTO2 considering the Ala140Asp and Asn142Asp SNPs have effect on stroke risk in conventional subgroups of hypertension, diabetes, smoking and obesity.

Subject Keywords

Ischemia., Cerebral ischemia., Cerebrovascular disease., Cardiovascular system, Glutathione transferase., Genetic polymorphisms.

URI

http://etd.lib.metu.edu.tr/upload/12616914/index.pdf
https://hdl.handle.net/11511/23361

Collections

Graduate School of Natural and Applied Sciences, Thesis