A single-nucleotide polymorphism in the human p27kip1 gene (-838C>A) affects basal promoter activity and the risk of myocardial infarction

BMC Biol. 2004 Apr 2:2:5. doi: 10.1186/1741-7007-2-5.

Abstract

Background: Excessive proliferation of vascular smooth muscle cells and leukocytes within the artery wall is a major event in the development of atherosclerosis. The growth suppressor p27kip1 associates with several cyclin-dependent kinase/cyclin complexes, thereby abrogating their capacity to induce progression through the cell cycle. Recent studies have implicated p27kip1 in the control of neointimal hyperplasia. For instance, p27kip1 ablation in apolipoprotein-E-null mice enhanced arterial cell proliferation and accelerated atherogenesis induced by dietary cholesterol. Therefore, p27kip1 is a candidate gene to modify the risk of developing atherosclerosis and associated ischaemic events (i.e., myocardial infarction and stroke).

Results: In this study we found three common single-nucleotide polymorphisms in the human p27kip1 gene (+326T>G [V109G], -79C>T, and -838C>A). The frequency of -838A carriers was significantly increased in myocardial infarction patients compared to healthy controls (odds ratio [OR] = 1.73, 95% confidence interval [95%CI] = 1.12-2.70). In addition, luciferase reporter constructs driven by the human p27kip1 gene promoter containing A at position -838 had decreased basal transcriptional activity when transiently transfected in Jurkat cells, compared with constructs bearing C in -838 (P = 0.04).

Conclusions: These data suggest that -838A is associated with reduced p27kip1 promoter activity and increased risk of myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclin-Dependent Kinase Inhibitor p27 / genetics*
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Jurkat Cells
  • Male
  • Middle Aged
  • Myocardial Infarction / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Transcription, Genetic

Substances

  • Cyclin-Dependent Kinase Inhibitor p27