Date

2015

Author

Öner, Tuğçe

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Stroke, as a neurological disorder, is defined as cessation or severe reduction of blood flow to the brain due to a clot or burst of blood vessel in the brain. Atherosclerosis is the hardening of the arteries due to accumulation of plaques in the vessels. Vitamin D deficiency is known as important risk factor in pathogenesis of atherosclerosis, which contributes to stroke development. Incidence of stroke is affected by environmental and genetic risk factors. So, genetic variations including single nucleotide polymorphisms (SNPs) in enzymes involved in Vitamin D metabolism can affect susceptibility to the development of the disease. Therefore, the primary aim of this study was to investigate the association between polymorphisms of Vitamin D metabolizing enzymes (rs927650 SNP in CYP24A1 and rs10741657 SNP in CYP2R1 genes) and the ischemic stroke risk. The study population was comprised of 256 ischemic stroke patients and 132 control subjects. There was no significant difference between two groups with regards to age and gender. It was found that when compared to control group, number of individuals with hypertension, diabetes, obesity and smoking was significantly higher in the group vi of ischemic stroke patients. Also, the average concentration of triglyceride and LDLcholesterol were higher in patients than controls. On the other hand, HDL-cholesterol level was significantly lower than controls. The frequency of risky T allele was almost same among ischemic stroke patients and control group for CYP24A1 rs927650 polymorphism. For CYP2R1 rs10741657 polymorphism, the frequency of risky G allele was found as 0.660 in patients and was nearly the same for controls. The study revealed no significant difference for distribution of genotypes for CYP24A1 rs927650 and CYP2R1 rs10741657 polymorphisms in any subgroups when compared between the stroke patients and controls (all P values were higher than 0.05). Detailed stratification analysis for CYP24A1 rs927650 SNP showed that, risk of having ischemic stroke for diabetic individuals was higher in risky T allele carrying individuals (OR=2.395) when compared with wild type genotype group (OR=2.275). In addition, the risk of smoking-related ischemic stroke was higher in risky T allele carriers (OR= 3.727). For CYP2R1 rs10741657 SNP, the risk of hypertensive, diabetic and obese individuals having ischemic stroke was significantly higher in G allele carriers when compared with wild type group (OR= 3.419, OR= 2.804 and OR= 4.817, respectively). Hypertension, smoking, obesity and LDL-cholesterol were found as significant predictors of ischemic stroke in logistic regression analysis; however it was revealed that HDL-cholesterol had protective effect on stroke. The association between rs927650 of CYP24A1 and rs10741657 of CYP2R1 polymorphisms and ischemic stroke risk in Turkish population was investigated in this study for the first time and it was concluded that there was no significant difference between patient and control groups with regard to C and T allele frequencies in CYP24A1 rs927650 polymorphism and A and G allele frequencies in CYP2R1 rs10741657 polymorphism.

Subject Keywords

Ischemia., Cytochrome P-450., Vitamin D., Genetic polymorphisms.

URI

http://etd.lib.metu.edu.tr/upload/12619562/index.pdf
https://hdl.handle.net/11511/25295

Collections

Graduate School of Natural and Applied Sciences, Thesis