Cdkn2a is an atherosclerosis modifier locus that regulates monocyte/macrophage proliferation.

ABSTRACT:

Objective

Common genetic variants in a 58-kb region of chromosome 9p21, near the CDKN2A/CDKN2B tumor suppressor locus, are strongly associated with coronary artery disease. However, the underlying mechanism of action remains unknown.

Methods and results

We previously reported a congenic mouse model harboring an atherosclerosis susceptibility locus and the region of homology with the human 9p21 locus. Microarray and transcript-specific expression analyses showed markedly decreased Cdkn2a expression, including both p16(INK4a) and p19(ARF), but not Cdkn2b (p15(INK4b)), in macrophages derived from congenic mice compared with controls. Atherosclerosis studies in subcongenic strains revealed genetic complexity and narrowed 1 locus to a small interval including Cdkn2a/b. Bone marro

SUBMITTER: Kuo CL 

PROVIDER: S-EPMC3350106 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature