Open Access Research article

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

Pelayo González1, Antonio Díez-Juan2, Eliecer Coto1*, Victoria Álvarez1, Julian R Reguero1, Alberto Batalla3 and Vicente Andrés2

Author Affiliations

1 Laboratorio de Genética Molecular, Instituto de Investigación Nefrológica (IRSIN-FRIAT), and Servicio de Cardiología, Hospital Universitario Central de Asturias (Maternidad), 33006 Oviedo, Spain

2 Laboratory of Vascular Biology, Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia-CSIC, 46010 Valencia, Spain

3 Servicio de Cardiología Hospital de Cabueñes, Gijón, Spain

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BMC Biology 2004, 2:5 doi:10.1186/1741-7007-2-5

Published: 2 April 2004

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.

Keywords:
myocardial infarction; p27kip1; single-nucleotide polymorphisms