Atherosclerosis 180 (2005) 305–309 Toll-like receptor 4 gene C119A but not Asp299Gly polymorphism is associated with ischemic stroke among ethnic Chinese in Taiwan Yi-Chun Lin a , Ying-Ming Chang a , Jia-Ming Yu a , Jeng-Hsien Yen b , Jan-Gowth Chang c , Chaur-Jong Hu a,d,∗ a Department of Neurology and Molecular Medicine Laboratory, Taipei Municipal Jen-Ai Hospital, No. 10 Jen-Ai Road, Sector 4, Taipei 106, Taiwan b Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan c Department of Medical Research and Clinical Pathology, China Medical University Hospital, Taichung, Taiwan d Brain Diseases and Aging Research Center, Taipei Medical University, Taipei, Taiwan Received 24 August 2004 Available online 25 April 2005 Abstract Stroke is one of the leading causes of death in the world. Most stroke patients are classified as having ischemic stroke. The causes of ischemic stroke are very diverse. Atherosclerosis resulting in cerebral or carotid arterial stenosis/occlusion plays the most important role in the occurrence of ischemic stroke. Inflammatory processes or immune responses are involved in the formation of atherosclerosis. Toll-like receptor 4 (TLR4) is a member of the toll-like receptor (TLR) family. TLRs are pattern-recognition receptors, which initiate innate immune responses after interaction with pattern-specific ligands. A polymorphism of the TLR4 gene, Asp299Gly, is associated with an increased risk for coronary heart diseases in Caucasian populations. In this study, we explored the complete coding regions of TLR4 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), Single-strand conformation polymorphism (SSCP), and sequencing and found obvious ethnic differences. There was no Asp299Gly polymorphism among the ethnic Chinese examined in this study. We found only one polymorphism on intron 1 (A119C) among our samples. The allele frequencies of 119A were 0.0256 and 0.0022 among the patients and controls, respectively. The odds ratio of 119A of TLR4 in ischemic stroke was 11.71 (95% CI: 1.52–90.01). This polymorphism was significantly associated with ischemic stroke. These data possibly implicate TLR4 as an important genetic factor for stroke in ethnic Chinese populations despite the rarity of the Asp299Gly polymorphism. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Toll-like receptor 4; Atherosclerosis; Asp299Gly 1. Introduction Cerebrovascular diseases including strokes are one of the leading causes of death worldwide. Ischemic stroke accounts for the majority of cerebrovascular diseases. Ischemic stroke usually results from atherosclerosis, heart disease, specific pathologies of small vessels (lacunar infarction), vasculitis, coagulation disorders, or other etiologies [1]. Atherosclerosis ∗ Corresponding author. Tel.: +886 2 27093600x5140; fax: +886 2 27046952. E-mail address: mimin@seed.net.tw (C.-J. Hu). induces arterial stenosis/occlusion, which can cause ischemic stroke as well as coronary artery heart disease (CAHD) and peripheral arterial occlusion disease. There has been much progress in understanding the pathophysiology of atheroscle- rosis [2–5]. The initial event of atherosclerosis is endothelial cell damage. Following this event, monocyte adhesion and migration occur, as well as smooth muscle cell proliferation [2]. There is compelling evidence supporting the involvement of inflammatory mediators or cytokines, such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8), in atherosclerosis formation [6,7]. Certain kinds of infection, such as Chlamydia, which induce inflammation, have been 0021-9150/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2004.12.022