K Gormley1, S Bevan, H S Markus. 1. Centre for Clinical Neuroscience, St. George's University of London, London, UK.
Abstract
BACKGROUND: Genetic variation in the renin-angiotensin system (RAS) has been implicated in stroke, particularly the small vessel disease (SVD) subtype. Furthermore, there may be two distinct subtypes of cerebral SVD, isolated lacunar infarction (ILI) and ischaemic leukoaraiosis (ILA). METHODS: 300 patients with well-phenotyped SVD and 600 controls were genotyped for five polymorphisms in the angiotensinogen (AGT) gene and eight polymorphisms within the angiotensin-converting enzyme (ACE) gene. RESULTS: AGT and ACE polymorphisms and haplotypes were no more common in SVD cases as a whole or the two subtypes. Amongst hypertensives only, an AGT promoter polymorphism (-20A-->C), was associated with the ILA subtype (multivariate odds ratio 1.716, 95% confidence interval 1.073-2.746, p = 0.024). CONCLUSIONS: RAS genetic variants are not strong risk factors for cerebral SVD. The AGT -20C allele may be a risk factor for the leukoaraiosis subtype amongst hypertensives.
BACKGROUND: Genetic variation in the renin-angiotensin system (RAS) has been implicated in stroke, particularly the small vessel disease (SVD) subtype. Furthermore, there may be two distinct subtypes of cerebral SVD, isolated lacunar infarction (ILI) and ischaemic leukoaraiosis (ILA). METHODS: 300 patients with well-phenotyped SVD and 600 controls were genotyped for five polymorphisms in the angiotensinogen (AGT) gene and eight polymorphisms within the angiotensin-converting enzyme (ACE) gene. RESULTS:AGT and ACE polymorphisms and haplotypes were no more common in SVD cases as a whole or the two subtypes. Amongst hypertensives only, an AGT promoter polymorphism (-20A-->C), was associated with the ILA subtype (multivariate odds ratio 1.716, 95% confidence interval 1.073-2.746, p = 0.024). CONCLUSIONS: RAS genetic variants are not strong risk factors for cerebral SVD. The AGT -20C allele may be a risk factor for the leukoaraiosis subtype amongst hypertensives.
Authors: A Vilar-Bergua; I Riba-Llena; C Nafría; A Bustamante; V Llombart; P Delgado; J Montaner Journal: J Cereb Blood Flow Metab Date: 2016-01 Impact factor: 6.200
Authors: Edith Hofer; Margherita Cavalieri; Joshua C Bis; Charles DeCarli; Myriam Fornage; Sigurdur Sigurdsson; Velandai Srikanth; Stella Trompet; Benjamin F J Verhaaren; Christiane Wolf; Qiong Yang; Hieab H H Adams; Philippe Amouyel; Alexa Beiser; Brendan M Buckley; Michele Callisaya; Ganesh Chauhan; Anton J M de Craen; Carole Dufouil; Cornelia M van Duijn; Ian Ford; Paul Freudenberger; Rebecca F Gottesman; Vilmundur Gudnason; Gerardo Heiss; Albert Hofman; Thomas Lumley; Oliver Martinez; Bernard Mazoyer; Chris Moran; Wiro J Niessen; Thanh Phan; Bruce M Psaty; Claudia L Satizabal; Naveed Sattar; Sabrina Schilling; Dean K Shibata; P Eline Slagboom; Albert Smith; David J Stott; Kent D Taylor; Russell Thomson; Anna M Töglhofer; Christophe Tzourio; Mark van Buchem; Jing Wang; Rudi G J Westendorp; B Gwen Windham; Meike W Vernooij; Alex Zijdenbos; Richard Beare; Stéphanie Debette; M Arfan Ikram; J Wouter Jukema; Lenore J Launer; W T Longstreth; Thomas H Mosley; Sudha Seshadri; Helena Schmidt; Reinhold Schmidt Journal: Stroke Date: 2015-10-08 Impact factor: 7.914