Abstract TP210: The Genetic Polymorphisms in Oxidative Stress Genes, Superoxide Dismutase and Glutathione Peroxidase, Correlated With Ischemic Stroke

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Abstract

Background: Reactive oxygen species (ROS) are controlled by endogenous antioxidant systems that include superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase and antioxidant vitamins. Defect in these systems may develop oxidative stress, and different studies have shown the profound effect of oxidative stress in the stroke because of high susceptibility of the brain to ROS-induced damage. Superoxide is dismutated to H2O2 by SOD which is further converted to H2O and O2 by GPx or catalase in the mitochondria and the lysosomes. The present study was aimed to investigate the association of SOD and GPx polymorphisms in the development of stroke.

Methods: A total 982 subjects ( 674 patients, 308 controls) were recruited in this study. Genotyping of SOD1 (rs1041740), SOD2 (rs4880), GPx1 (rs1050450) were performed by LightCycler real-time PCR using LightSNiPreagents and FastStartDNAMasterHybProbe while genotyping of GPx4 (rs713041) were done by PCR-RFLP were done by PCR-RFLP. All biochemical parameter were measured in automated clinical chemistry analyzer, at department of laboratory medicine.

Results: Our study demonstrated that the CC+CT/TT genotype of rs4880 significantly increased the risk of stroke (AOR=1.57, 95%CI=1.10-2.24) and SAD-stroke (AOR=1.64, 95%CI=1.17-2.41) compared with CC genotype. In GPx polymorphsims, rs1050450 showed no association with stoke, while rs713041 and the combination analysis of rs1050450 with rs713041 demonstrated the significant association for the stroke development. Interestingly, the inter-combined effect of genetic polymorphism of SOD/GPx showed the significant association for the stroke. Most of the genotypes of these SNPs demonstrated significant difference between control and stroke cases on different biochemical parameters.

Conclusion: This study suggests a possible role for oxidative stress in the risk of stroke and clearly states that genetic component of stroke is polygenic as altered SOD and GPx genes interaction showed increased risk for stroke development

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