Association between TNFRSF11B gene polymorphisms and history of ischemic stroke in Italian diabetic patients
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ORIGINAL INVESTIGATION
Association between TNFRSF11B gene polymorphisms and history of ischemic stroke in Italian diabetic patients Federico Biscetti • Giuseppe Straface • Silvia Giovannini • Angelo Santoliquido Flavia Angelini • Luca Santoro • Carlo Filippo Porreca • Giovanni Pecorini • Giovanni Ghirlanda • Andrea Flex
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Received: 24 April 2012 / Accepted: 29 August 2012 / Published online: 11 September 2012 Ó Springer-Verlag 2012
Abstract Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. The present study aimed to evaluate whether OPG gene (TNFRSF11B) polymorphisms are involved in ischemic stroke in an Italian population with diabetes. Participants in a retrospective case–control study included 364 diabetic patients (180 males, 184 females) with history of ischemic stroke and 492 diabetic subjects without history of ischemic stroke (252 males, 240 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism. We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were F. Biscetti C. F. Porreca G. Pecorini G. Ghirlanda A. Flex (&) Department of Medicine, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy e-mail: [email protected] F. Biscetti F. Angelini C. F. Porreca G. Pecorini G. Ghirlanda A. Flex Laboratory of Vascular Biology and Genetics, Catholic University School of Medicine, Rome, Italy G. Straface Vascular Medicine and Atherothrombosis Laboratory, Department of Experimental Medicine, Sapienza University of Rome, Polo Pontino, Italy S. Giovannini Department of Gerontology and Geriatrics, A. Gemelli University Hospital, Catholic University School of Medicine, Rome, Italy A. Santoliquido L. Santoro Department of Internal Medicine, Complesso Integrato Columbus, School of Medicine, Rome, Italy
significantly (34.1 vs. 9.5 %, P \ 0.0001; 30.8 vs. 6.3 %, P \ 0.0001 and 26.4 vs. 11.6 % P \ 0.0001, respectively) and independently (adjusted OR 5.15 [3.46–7.68], OR 6.63 [4.26–10.31], and OR 3.03 [2.04–4.50], respectively) associated with history of ischemic stroke. We also found that these three polymorphisms act synergistically in patients with stroke history. The TNFRSF11B gene polymorphisms studied are associated with history of ischemic stroke and synergistic effects between these genotypes might be potential markers for cerebrovascular disorders.
Introduction Ischemic cerebrovascular disease is a heterogeneous multifactorial disease thought to result from both genetic and conventional risk factors (Dichgans 2007; DominguesMontanari et al. 2008). The development of ischemic stroke has been attributed to the interaction of multiple factors, including genetic variants, chronic diseases, risk behaviors, and inflammation (Hassan and Markus 2000; Elkind 2010; Ross 1999; Hansson 2005, Petrovic et al. 2003; Tuttolomondo et al. 2012; Santl Letonja
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