%0 Journal Article
%T A single-nucleotide polymorphism in the human p27kip1 gene (-838C>A) affects basal promoter activity and the risk of myocardial infarction
%A Pelayo Gonz¨˘lez
%A Antonio D¨Şez-Juan
%A Eliecer Coto
%A Victoria ¨˘lvarez
%A Julian R Reguero
%A Alberto Batalla
%A Vicente Andr¨¦s
%J BMC Biology
%D 2004
%I BioMed Central
%R 10.1186/1741-7007-2-5
%X 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¨C2.70). 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).These data suggest that -838A is associated with reduced p27kip1 promoter activity and increased risk of myocardial infarction.The proliferation of leukocytes and vascular smooth muscle cells (VSMCs) within the artery wall is a hallmark of the atherosclerotic process [1]. The exposure of coronary arteries to chemical and mechanical injury triggers an inflammatory response characterized by excessive arterial cell proliferation. Progression through the cell cycle depends on the sequential activation of several cyclin-dependent kinases (CDKs). Activation of CDKs requires their interaction with regulatory subunits named cyclins. In resting cells, cyclin¨CCDK complexes are inhibited by the reversible association with CDK inhibitory proteins (CKIs) of the Cip/Kip family (p21cip1, p27kip1, and p57kip2) and Ink4 family (p16Ink4a, p15Ink4b, p18Ink4c, p19Ink4d) [2].In recent years, accumulating evidence has implicated p27kip1 as an important endogenous regulator of leukocyte and VSMC proliferation in various pathophysiological situations [3-7]. Remarkably, p27kip1 expression and proliferation of VSMCs and leukocytes are inversely correlated in human atheroma, and a significantly lower level of p27kip1 expression has been reported in primary atherosclerotic and restenotic tissue versus nondiseased arterial tissue [8-10]. We have previously shown that fat-fed mice deficient in both apolipoprotein E (a
%K myocardial infarction
%K p27kip1
%K single-nucleotide polymorphisms
%U http://www.biomedcentral.com/1741-7007/2/5