The 9p21 locus and its potential role in atherosclerosis susceptibility; molecular mechanisms and clinical implications

Amir Tajbakhsh, Mohammad Sadegh Khorrami, Seyed Mahdi Hassanian, Malihe Aghasizade, Alireza Pasdar, Mina Maftouh, Ehsan Tabatabai, Seyed Mohammad Reza Parizadeh, Mostafa Fazeli, Gordon A. Ferns, Majid Ghayour-Mobarhan, Amir Avan*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5730-5737
Number of pages8
JournalCurrent Pharmaceutical Design
Volume22
Issue number37
DOIs
Publication statusPublished - 1 Oct 2016

Keywords

  • 9p21 locus
  • Biomarkers
  • Coronary artery disease
  • Risk stratification

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