title: Angiotensin II type-1 receptor A1166C polymorphism is associated with increased risk of ischemic stroke in hypertensive smokers.
abstract: Recent observations revealed a novel role of angiotensin-converting enzyme 2 and the angiotensin II type-1 receptor (AT1R) in lung injury, thereby extending knowledge about the functions of the angiotensin system. Angiotensin II, whose target is the AT1R, is a potent vasoconstrictor. Accordingly, an imbalance leading to enhanced activity of the angiotensin II-AT1R axis is postulated to contribute to both circulatory disturbances and lung injury. In this context, a functional single-nucleotide polymorphism, AT1R A1166C, which leads to enhanced responsiveness of the AT1R, has been postulated as a candidate susceptibility factor for ischemic stroke. The aim of our study was to investigate its occurrence in ischemic stroke and to analyze its possible synergistic associations with clinical risk factors. Genetic and clinical data on 308 consecutive patients with acutely developing ischemic stroke were analyzed. A total of 272 stroke and neuroimaging alteration-free subjects served as a control group. Univariate and logistic regression statistical approaches were used. Alone, the AT1R 1166C allele did not pose a risk of stroke. In hypertensive smokers, however, it was associated with an increased risk of ischemic stroke (OR 22.3, 95% CI 5.8-110.2, p<0.001). Further subgroup analysis revealed the same association for both small-vessel (OR 24.3, 95% CI 6.1-121.1, p<0.001) and large-vessel (OR 21.3, 95% CI 4.6-81.1, p<0.001) infarction. On a pathophysiological basis, our results suggest the possibility that the AT1R A1166C polymorphism might give rise to ischemic stroke indirectly via an unfavorable effect on the cardiorespiratory function.
authors.affiliation: Department of Neurology and Neurophysiology, Pándy Kálmán County Hospital, Gyula, and Department of Medical Genetics and Child Development, University of Pécs, Hungary. szolnoki99@hotmail.com
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Szolnoki
authors.forename: Viktória
authors.initials: V
authors.lastname: Havasi
authors.forename: Gábor
authors.initials: G
authors.lastname: Talián
authors.forename: Judit
authors.initials: J
authors.lastname: Bene
authors.forename: Katalin
authors.initials: K
authors.lastname: Komlósi
authors.forename: Ferenc
authors.initials: F
authors.lastname: Somogyvári
authors.forename: András
authors.initials: A
authors.lastname: Kondacs
authors.forename: Mihály
authors.initials: M
authors.lastname: Szabó
authors.forename: Lajos
authors.initials: L
authors.lastname: Fodor
authors.forename: Anita
authors.initials: A
authors.lastname: Bodor
authors.forename: Béla
authors.initials: B
authors.lastname: Melegh
mesh_terms: D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D012907:Smoking; D020521:Stroke / Q000235:genetics*
chemical_list: D044140:Receptor, Angiotensin, Type 1