The relationship between plasma t-PA and PAI-1 levels is dependent on epistatic effects of the ACE I/D and PAI-1 4G/5G polymorphisms

Jason H. Moore*, M. E. Smolkin, J. M. Lamb, N. J. Brown, D. E. Vaughan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Thrombus formation and degradation is partly due to a complex interplay between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1). There is accumulating evidence that plasma levels of t-PA and PAI-1 may be influenced by an interaction between the fibrinolytic and renin-angiotensin systems. The goal of this study was to conduct an exploratory data analysis to determine whether there is evidence that the relationship (i.e. correlation) between plasma t-PA and PAI-1 is influenced by interactive effects of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) and plasminogen activator inhibitor 1 (PAI-1) 4G/5G polymorphisms in a sample of 50 unrelated African Americans and 117 unrelated Caucasians. In a single-locus analysis, no evidence for heterogeneity of plasma t-PA and PAI-1 correlations among either ACE I/D or PAI-1 4G/5G genotypes was detected. However, using the combinatorial partitioning method for exploratory data analysis, we identified evidence that is suggestive of heterogeneity of plasma t-PA and PAI-1 correlations among multilocus ACE I/D and PAI-1 4G/5G genotypes in African American females, Caucasian females, Caucasian males, but not African American males. From these results, we propose as a working hypothesis that the correlation between plasma t-PA and PAI-1 may be dependent on epistatic effects of the ACE I/D and PAI-1 4G/5G polymorphisms. This study supports the idea that interactions between the fibrinolytic and renin-angiotensin systems play an important role in the genetic architecture of plasma t-PA and PAI-1.

Original languageEnglish (US)
Pages (from-to)53-59
Number of pages7
JournalClinical Genetics
Volume62
Issue number1
DOIs
StatePublished - Jul 1 2002

Keywords

  • Combinatorial partitioning method
  • Correlation
  • Epistasis
  • Fibrinolytic system
  • Gene-gene interaction
  • Reninangiotensin system

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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