The UCP2-866G/A Polymorphism Could be Considered as a Genetic Marker of Different Functional Prognosis in Ischemic Stroke After Recanalization

• Published in: Neuromolecular medicine Vol. 19; no. 4; pp. 571 - 578
• Main Authors: Díaz-Maroto Cicuéndez, I., Fernández-Díaz, E., García-García, J., Jordán, J., Fernández-Cadenas, I., Montaner, J., Serrano-Heras, G., Segura, T.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2017; Springer Nature B.V
• Subjects: Animal models; Biomedical and Life Sciences; Biomedicine; Cerebral blood flow; Energy metabolism; Gene polymorphism; Genetic markers; Genotype & phenotype; Internal Medicine; Intravenous administration; Ischemia; Membrane proteins; Mitochondria; Mitochondrial uncoupling protein 2; Neurology; Neurosciences; Occlusion; Original Paper; Polymerase chain reaction; Prognosis; Reactive oxygen species; Reperfusion; Restriction fragment length polymorphism; Stroke; Thrombolysis; Transcription; Ultrasound; PCR–RFLP; Single nucleotide polymorphism; Thrombolysis; Stroke, ischemic; Reperfusion injury; Revascularization
• ISSN: 1535-1084; 1559-1174
• DOI: 10.1007/s12017-017-8470-x

Recent studies based on experimental animal models of stroke have suggested that uncoupling protein 2 (UCP2), an inner mitochondrial membrane protein that is thought to regulate energy metabolism and reduce reactive oxygen species generation, provides protection against reperfusion damage. We aimed to investigate whether -866G/A polymorphism in the promoter of the UCP2 gene, which enhances its transcriptional activity, is associated with functional prognosis in patients with embolic ischemic stroke after early recanalization. We investigate a hospital-based prospective cohort of patients with acute ischemic stroke due to occlusion of the middle cerebral artery diagnosed by transcranial Doppler who obtained a partial/complete recanalization 24 h after administration of intravenous thrombolysis. The main end point of the study was functional independence defined as modified Rankin Scale 0–2 on day 90. A total of 80 patients were enrolled. The UCP2-866G/A polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism technique (14 genotype A/A (18%), 45 genotype A/G (56%) and 21 genotype G/G (26%). The percentage of patients with good functional outcome at 3 months was significantly higher in patients harboring the A/A genotype than in those with A/G or G/G genotypes (85 vs 41%, p  = 0.01). The A/A genotype was found to be an independent marker of good prognosis after adjustment for secondary variables (age, sex, glucose level, NIHSS score at baseline, complete recanalization and early neurological improvement) in a logistic regression analysis (OR 0.05, 95% CI 0.01–0.48, p  = 0.01). Our results suggest that the AA genotype of UCP2-866 may predict a better functional outcome in ischemic stroke after recanalization of proximal MCA occlusion.