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(Stroke. 2003;34:2828.)
© 2003 American Heart Association, Inc.

Original Contributions

Editorial Comment— Genetic Make-Up for Increased PAI-1 Expression Protects Against Stroke

Research Laboratory of the Department of Clinical Chemistry, Utrecht University Medical School, Utrecht, the Netherlands
Department of Internal Medicine, Utrecht University Medical School, Utrecht, the Netherlands

An extract of the first 250 words of the full text is provided, because this article has no abstract.

This issue of Stroke reports findings that the 4G variant of the PAI-1 4G/5G polymorphism is associated with a reduced incidence of stroke.¹ Those findings are in agreement with 7 other studies that observed a similar relationship between the 4G variant of PAI-1 and a reduced stroke risk.^2–8 This consistency in 8 independent studies minimizes the possibility that the relationship between the PAI-1 4G variant of PAI-1 and reduced stroke risk is a chance finding.

PAI-1 4G/5G is an interesting "functional" polymorphism because the alleles are the real cause of variation in PAI-1 expression.⁹ The 4G allele of the PAI-1 4G/5G polymorphism lacks a binding site for a transcription repressor protein, which is present on the 5G allele. Therefore, the 4G is the high PAI-1 expresser allele and the 5G the low expresser allele. Subjects who are homozygous for the 4G allele have 25% higher plasma concentrations than subjects homozygous for the 5G allele.⁹ Those findings indicate that homozygosity for the 4G allele stands for lifelong exposure to increased PAI-1 expression. The PAI-1 4G/5G polymorphism is an important tool in investigating the etiological involvement of PAI-1 in stroke because genetic make-up is fixed at conception; therefore, an association between genetic make-up for increased PAI-1 expression (PAI-1 4G allele) and a reduced risk of stroke is not confounded by other risk factors of stroke.¹⁰ For the same reason, genetic make-up for high PAI-1 expression is not a consequence of stroke. A relationship between the PAI-1 4G allele and a reduced risk . . . [Full Text of this Article]

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