Hindawi Publishing Corporation Disease Markers Volume 35 (2013), Issue 6, Pages 641–646 http://dx.doi.org/10.1155/2013/769574 Research Article Association of Functional VKORC1 Promoter Polymorphism with Occurrence and Clinical Aspects of Ischemic Stroke in a Greek Population Georgia Ragia, 1 Stella Marousi, 2 John Ellul, 2 Vangelis G. Manolopoulos, 1 and Anna Tavridou 1 1 Laboratory of Pharmacology, Medical School, Democritus University of hrace, Dragana Campus, 68100 Alexandroupolis, Greece 2 Department of Neurology, University of Patras, Rion, 26500 Patras, Greece Correspondence should be addressed to Anna Tavridou; atavrid@med.duth.gr Received 30 June 2013; Revised 25 September 2013; Accepted 9 October 2013 Academic Editor: Ralf Lichtinghagen Copyright © 2013 Georgia Ragia et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Genetic factors are considered to play an important role in determining the susceptibility to the occurrence, clinical course, and functional outcome of an acute ischemic stroke (IS). Undercarboxylation of speciic vitamin K-dependent proteins, due to genetic polymorphisms of VKORC1, can afect both vascular calciication and thrombogenicity. We sought to determine the association of VKORC1 −1639G > A polymorphism with IS incidence, age of onset, severity of disease, and functional outcome ater an acute IS. VKORC1 −1639G > A polymorphism was determined in 145 consecutive patients with irst ever IS and 145 age- and sex-matched control subjects of Greek Caucasian origin using PCR-RFLP. Stroke severity and functional outcome were assessed on admission and at one month ater stroke, respectively. Frequency of VKORC1 −1639G > A genotypes did not difer between IS patients and controls (OR = 1.12,  = 0.51). Moreover, carriage of the A allele was not associated with age of stroke onset, severity of disease (Scandinavian stroke scale score 32.2 versus 32.9, resp.,  = 0.96), or poor outcome at 1 month post-stroke (52.9 versus 64.4%, resp.,  = 0.31). In conclusion, VKORC1 −1639G > A polymorphism is not a genetic determinant of IS occurrence, age of onset, severity, or functional outcome of disease in a Greek population. 1. Introduction Ischemic stroke (IS), a multifactorial disease which shares many common risk factors with coronary artery disease, leads to a high mortality and disability rate [1]. However, distinct mechanisms may be critical in the development of acute ischemic coronary and cerebrovascular events. Both environmental and genetic factors are considered to play important role in determining the susceptibility to the occur- rence, clinical course, and functional outcome of an acute IS. here is evidence that common variants in several genes, each exerting a modest efect, contribute to the risk of stroke [2]. Vitamin K-dependent proteins play a signiicant role in coagulation but also in bone metabolism and vascular calcii- cation. Modiication by -carboxylation is necessary for vita- min K-dependent proteins to become biologically active [3]. Vitamin K epoxide reductase complex subunit 1 (VKORC1) is involved in this process by mediating recycling of vitamin K 2,3 epoxide to vitamin K hydroquinone [4], a cofactor for the conversion of glutamate to -carboxyglutamic acid. VKORC1 is the target of coumarin derivatives, and several genetic variations of the VKORC1 gene inluence response to anticoagulant therapy (for review, see [5]). Matrix Gla protein (MGP), a vitamin K-dependent protein, is important in the prevention of vascular calciication since MGP-deicient mice sufer extensive media calciication of the aorta [6]. Inhibition of VKORC1 by warfarin results in undercarboxylation of MGP and subsequent media calciication in rat arteries and heart valves [7]. Single-nucleotide polymorphisms (SNPs) of VKORC1 have been associated with a higher risk of arterial vascular disease, including stroke, in a Chinese population [8], and a signiicantly higher risk of aortic calciication [9]. How- ever, two subsequent studies in German cohorts did not