837e4a63-1327-4c49-83d5-eb27f943dfb0
title
A single-nucleotide polymorphism in the human  p27kip1  gene ( -838C>A ) affects basal promoter activity and the risk of myocardial infarction.
222452ac-9d30-491d-8c3d-fa94695ad488
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.