title: The 9p21 Locus and its Potential Role in Atherosclerosis Susceptibility; Molecular Mechanisms and Clinical Implications.
abstract: Cardiovascular disease (CVD) is the leading cause of global mortality. Although extensive efforts have been made to identify valid biomarkers for CVD risk, relatively few are of proven clinical utility. It is recognized that genetic factors play a major role in determining the susceptibility to CVD. Recent genome-wide-association-studies have demonstrated common genetic variants in a region on chromosome 9p21 associated with an increased risk of CVD. Several genetic-polymorphisms have been identified in this region that are highly associated with CVD, and these are clustered around the gene loci for CDKN2B (coding for p15ink4b), CDKN2A (coding for p16ink4a and p14ARF) and the 3' end of CDKN2BAS, which has been termed antisense noncoding RNA in the INK4 locus (ANRIL). Targeted deletion of the 9p21 locus reduces the cardiac expression of CDKN2A/B and is the most frequent mechanism for methylthioadenosine phosphorylase inactivation, leading to a less stable plaque phenotype in the artery. Further investigations will be essential to explore the clinical utility of emerging-markers in larger and multicenter setting in order to establish their values for risk stratification or prediction a chance of future CVD events. The aim of the current review was to provide an overview of the possible molecular mechanisms by which the chromosome 9p21 locus may confer CVD risk, and the consequential clinical implications with particular emphasis on preclinical/clinical trials on genetic changes of this locus and CVD risk.
authors.forename: Amir
authors.initials: A
authors.lastname: Tajbakhsh
authors.forename: Mohammad Sadegh
authors.initials: MS
authors.lastname: Khorrami
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Hassanian
authors.forename: Malihe
authors.initials: M
authors.lastname: Aghasizade
authors.forename: Alireza
authors.initials: A
authors.lastname: Pasdar
authors.forename: Mina
authors.initials: M
authors.lastname: Maftouh
authors.forename: Ehsan
authors.initials: E
authors.lastname: Tabatabai
authors.forename: Seyed Mohammad Reza
authors.initials: SM
authors.lastname: Parizadeh
authors.forename: Mostafa
authors.initials: M
authors.lastname: Fazeli
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Ferns
authors.affiliation: Biochemistry of Nutrition Research Center; School of Medicine, Mashhad University of Medical Sciences, Mashhad.
authors.forename: Majid
authors.initials: M
authors.lastname: Ghayour-Mobarhan
authors.affiliation: Molecular Medicine Group, Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Avan
mesh_terms: D050197:Atherosclerosis / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics*; D006801:Humans; D010641:Phenotype