β Fibrinogen gene -455 G/A polymorphisms as Determinants of Ischemic Stroke Outcome Severity in Response to Aspirin Treatment Kiking Ritarwan 1 *, Tri Widyawati 2 , Aznan Lelo 2 1 Neurology Department, Faculty of Medicine/ Adam Malik General Hospital, University of Sumatera Utara, Bunga Lau Street no 17, Medan Tuntungan, Medan-20136, Indonesia 2 Pharmacology and Therapeutic Department, Faculty of Medicine, University of Sumatera Utara, dr. Mansyur Street no 5, Medan-20155, Indonesia Abstract : Stroke is a leading cause of disability and death. For secondary treatment, aspirin is the agent of choice. Polymorphisms in the promoter region of β fibrinogen gene -455 G/A are associated with increased plasma fibrinogen levels. We evaluated the correlation between β fibrinogen gene-455 G/A promoter polymorphisms and ischemic stroke (IS) outcome on modified Rankin Scale (mRS) in patients treated with aspirin by age groups. A Cohort study design was adopted comprising 136 patients of younger (<55) and older ages (>55). Patients used aspirin for 3 months after IS and completed a detailed stroke-outcome questionnaire. Overall, genotype distribution was 66.2% for GG, 27.2% for GA and 6.6% for AA. The young- age group showed genotypes GG, GA and AA as 30.1%, 15.4% and 6.6%, respectively. After aspirin administration, plasma fibrinogen levels dropped to 248.65±100.71 mg/dl and 235.75±82.01 mg/dl in young and old age groups, respectively. Low and high plasma fibrinogen levels were determined on mRS with a cut-off value of 268.05 mg/dl. In a logistic regression model, the -455 G/A locus genotype showed a significant correlation with age and plasma fibrinogen levels on mRS at day 0 (P<0.25). Poisson Confidence Intervals (PCI) were calculated. Age relative risk was 0.67 (PCI: 0.30-1.49), while fibrinogen-mRS relative risk was 0.78 (PCI: 0.37 – 1.63) at day 0. Aspirin significantly (P<0.05) decreased plasma fibrinogen levels in correlation with promoter polymorphisms in an age-dependent fashion. Significant differences between high and low plasma fibrinogen levels before and after the use of aspirin coincided with substantially reduced mRS scores. Keywords: β fibrinogen -455 FGB; aspirin; stroke outcome; ischemic stroke risk. Introduction Stroke ranks third after ischemic heart disease and cancer as a cause of life-long disability in high- income countries and as a cause of death worldwide. 1 The incidence of stroke varies depending on the country and increases exponentially with age. In Western societies, about 80% of stroke events are due to focal cerebral ischemia secondary to arterial occlusion. The remaining 20% are associated with incident hemorrhage. 2 Ischemic brain injury is thought to result from a cascade of events starting with energy depletion and ending in cell death. The intermediate factors include an excess of extracellular excitatory amino acids, formation of free radicals, and inflammation. 3,4 International Journal of PharmTech Research CODEN (USA): IJPRIF, ISSN: 0974-4304 Vol.9, No.4, pp 147-152, 2016