Tissue Plasminogen Activator −7351C/T Polymorphism and Lacunar Stroke

Abstract

To the Editor: Jannes et al1 reported that a polymorphism in the tissue plasminogen activator (tPA) gene (−7351C/T) was associated with ischemic stroke in an Australian population. Stratification for stroke subtype demonstrated an association with lacunar infarction (OR: 2.7; 95% CI, 1.1 to 6.7), but not with other stroke subtypes. The authors interpreted this result as providing evidence that fibrinolytic factors play an important role in maintaining small vessel patency. The polymorphism is located within the binding site for the transcription factor Sp1, in the enhancer region of the tPA gene,1 and the TT genotype has been associated with significantly reduced vascular tPA release rates.2 This association could give clues to the pathogenesis of lacunar stroke, but first replication in independent populations is important, particularly because the original association was found in a small sample size, with only 43 patients in the lacunar subgroup. Therefore, we attempted to replicate it in a prospectively collected group of patients with well-phenotyped lacunar stroke. In addition, we determined whether the polymorphism predisposed to 1 particular type of lacunar stroke. It has been suggested that patients with larger lacunar infarcts (isolated lacunar infarction [ILI]) without leukoaraiosis may have microatheroma at the origins and proximal portions of the perforating arteries. In contrast, patients with lacunar infarction and confluent leukoaraiosis (ischemic leukoaraiosis [ILA]) may have a diffuse arteriopathy affecting the smaller perforating vessels.3 Previous studies have suggested different genetic associations in the 2 groups.4 Three hundred …