Background: Ischemic stroke (IS) is one of the main causes of death worldwide. It is worthy to attempt to identify genes that acts as risk factors for IS for early prediction and primary prevention that may reduce its incidence. Aim of the study was to determine the relation between interleukin-18 (IL-18) (
607 C/A) and (
137 G/C) polymorphisms and the risk of IS in Egyptian patients. In parallel, to analyze these polymorphisms as risk factors for large-vessel versus small-vessel diseases. Patients and methods: A total of 120 subjects (60 IS patients and 60 healthy controls) were recruited to the study. Genotypic analysis of IL-18 promoter polymorphisms were performed using sequencespecific primers- polymerase chain reaction (SSP-PCR) method. Results: For IL-18 (
607 C/A) polymorphism, a significant higher risk of IS was related to the AA genotype (odd ratio (OR) = 5.38, P = 0.004,) and A allele (OR = 2.07, P = 0.006), than in controls. Whereas, for IL-18 (
137 G/C) polymorphism, a significant lower risk of IS was related to the GC genotype (OR = 0.17, P < 0.001) and C allele (OR = 0.37, P < 0.001) than in controls. Moreover, both polymorphisms did not exhibit any significant differences between large vessel (LV) and small vessel (SV) disease of IS (P > 0.05). In addition, the haplotype analysis showed non-significant differences between IS patients and controls (P > 0.05). Conclusion: This study concludes that IL-18
607AA genotype and A allele may be risk factors to IS, whereas IL-18
137 GC genotype and C allele may be protective factors against IS in Egyptian population.