Pharmacogenetic Determinants of Beta-fibrinogen Gene Polymorphism in Response to Aspirin in Patients with Severe Ischemic Stroke
Sembiring, Rosita J.
Sadewa, Ahmad H.
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Objective: Carrier of the A allele in the −455 locus of the beta-fibrinogen gene’s promoter region has previously been shown to be associated with elevated fibrinogen levels. The relationship between fibrinogen gene polymorphism and outcome in subjects receiving aspirin therapy is not clear; because it is biologically plausible that a pro-thrombotic polymorphism may exert a differential effect across different ages, this study was classified into young and old aged participants. Materials and Methods: A cohort study design is comprising 136 consecutive patients was done. All patients with acute ischemic stroke who were admitted to Adam Malik Hospital were divided into two groups as below and above the age of 55 years. Subjects received anti-platelet aspirin for 3 months. Genomic DNA was extracted from peripheral blood lymphocytes using standard protocol. Plasma fibrinogen level and modified Rankin Scale (mRS) were determined, and cerebral imaging was performed. Results: Genotype distributions among the total population (n = 136) were 66.2% for GG, 27.2% for GA and 6.6% for AA; at young age, these distributions were found 30.1%, 15.4% and 6.6%, respectively. After administration of aspirin, plasma fibrinogen levels were found to be 248.65 ± 100.71 and 235.75 ± 82.01 mg/dl, respectively for young and old age; the cut-off value of plasma fibrinogen concentration was 268.05 mg/dl. In a logistic regression model, the −455 G/A locus genotype showed a significant interaction between age and fibrinogen level in mRS of day 0. The identified relative risk (RR) on age and fibrinogen level was 0.67 (0.30-1.49) and 0.78 (0.37-1.63), respectively. Conclusion: Plasma fibrinogen levels decreased after administration of either aspirin or polymorphisms according to age. Identification of stroke risk factors based on the RR of plasma fibrinogen levels are at higher degree in younger age.