Investigation of gene polymorphisms associated with intracranial aneurysm in Turkish patients

Intracranial aneurysms (IA) are balloon like dilation of the intracranial arterial wall in the brain. It affects %2-5 of the general population and arise from the action of multiple genetic and environmental risk factors. Single nucleotide polymorphisms (SNPs) are variations at a single position in a DNA sequence among individuals and they are associated with certain diseases to evaluate an individual's genetic predisposition to develop a disease. Recently, several SNPs associated with IA have been identified in genome-wide association studies. To our knowledge, the effects of these SNP's in Turkish population has not been studied and this arises great necessity to study them. With this thesis study it is aimed to genotype and analyze 15 different polymorphisms, known to be associated with IA in different populations, to determine genetic risk predisposition of these SNPs in Turkish population. Genotyping of 15 SNPs was performed in 208 samples (105 patients, 103 controls) by iPLEX method. Hardy Weinberg Equilibrium was tested for each of 15 SNPs and it is obtained that all genotype frequencies was at HWE (p≤0,05). The association of SNP alleles and genotypes with intracranial aneurysm was investigated and it is found that SNPs which studied in this thesis have no statistically association with intracranial aneurysm in our population (OR>1, p≤0,05). Associations between genotypes of SNPs and clinical-demographic variables were investigated and SNPs that found to be statistically associated with history of cardiovascular diesease was rs6538595; with family history of intracranial aneurysm were rs9315204 and rs10757278; with smoking were rs1333040, rs1429412, rs10757272 and rs10757278 (p≤0,05). Logistic regression analyses were used to ascertain the effects of clinical-demographic factors and genotypes in the intracranial aneurysm susceptibility and with this assessment gender, family history of intracranial aneurysm and smoking were found to be significant risk factors for intracranial aneurysm in study group. Consequently, with this study multiple SNPs in multiple sample associated with intracranial aneurysm for the first time in our population.