title: Association of C3435T multi drug resistance gene-1 polymorphism with aspirin resistance in ischemic stroke and its subtypes.
abstract: Aspirin is the most commonly used antiplatelet drug for treatment of a serious vascular event, most notably myocardial infarction and stroke. Significant fraction of aspirin treated patients is resistant to the antiplatelet effects of the drugs. Previous studies have suggested that a genetic basis for aspirin resistance exists. Therefore the present study was taken up to investigate the role of C3435T polymorphism (rs 1045642) of multiple drug resistance-1 (MDR-1) gene with aspirin resistance in stroke patients. Five hundred and sixty ischemic stroke patients and 560 age and sex matched healthy controls were involved in the study. Baseline clinical data were collected and follow-up telephone interviews were conducted with patients at 3, 6 and 12 months post event to determine stroke outcome. Blood samples were collected and genotypes determined. Significant difference was observed in the genotype distribution and allele frequency between patients and controls. The results were confirmed by a step wise multiple logistic regression analysis controlling all other confounding risk factors [adjusted Odds ratio=3.132 (95% CI; 2.043-4.800; p<0.001)]. There was a significant difference in genotype distribution between drug responders and non-responders. The risk of aspirin resistance was significantly high in patients with TT genotype in comparison to those with CC genotype [(TT vs. CC, χ(2)=6.268; p=0.012, Odds ratio=1.85) (95% CI; 1.142-3.017) (adjusted Odds ratio=2.465; 95% CI; 1.895-4.625 and p<0.001)]. As far as the stroke subtypes are concerned TT genotype associated significantly with aspirin resistance in intracranial large artery atherosclerosis. Our results indicate that the risk of aspirin resistance is more in patients with 3435TT genotype than in those with CC genotype. However, this is a preliminary study and a large study of replication is needed to confirm our results.
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad-500016, India.
authors.forename: Vandana
authors.initials: V
authors.lastname: Sharma
authors.forename: Subhash
authors.initials: S
authors.lastname: Kaul
authors.forename: Amal
authors.initials: A
authors.lastname: Al-Hazzani
authors.forename: T Surya
authors.initials: TS
authors.lastname: Prabha
authors.forename: Polugari Prem Kumar Manohar
authors.initials: PP
authors.lastname: Rao
authors.forename: Sneha
authors.initials: S
authors.lastname: Dadheech
authors.forename: A
authors.initials: A
authors.lastname: Jyothy
authors.forename: Anjana
authors.initials: A
authors.lastname: Munshi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000145:classification / Q000235:genetics* / Q000517:prevention & control; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020521:Stroke / Q000145:classification / Q000235:genetics* / Q000517:prevention & control
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001241:Aspirin