Functional genomics of the CDKN2A/B locus in cardiovascular and metabolic disease: what have we learned from GWASs?
Genome-wide association studies (GWASs) provide an unprecedented opportunity to examine, on a large scale, the association of common genetic variants with complex diseases like type 2 diabetes (T2D) and cardiovascular disease (CVD), thus allowing the identification of new potential disease loci. Using this approach, numerous studies have associated SNPs on chromosome 9p21.3 situated near the cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) locus with the risk for coronary artery disease (CAD) and T2D. However, identifying the function of the nearby gene products (CDKN2A/B and ANRIL) in the pathophysiology of these conditions requires functional genomic studies. We review the current knowledge, from studies using human and mouse models, describing the function of CDKN2A/B gene products, which may mechanistically link the 9p21.3 risk locus with CVD and diabetes.
University of Lille, F-59000, Lille, France; Inserm, U1011, F-59000, Lille, France; European Genomic Institute for Diabetes (EGID), FR3508, Lille, France; Institut Pasteur de Lille, F-59019, Lille, France; Centre National de la Recherche Scientifique (CNRS), UMR 8199, Lille, France.
Sarah Anissa
SA
Hannou
Cardiovascular Research Institute Maastricht (CARIM), Department of Internal Medicine, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands.
Kristiaan
K
Wouters
University of Lille, F-59000, Lille, France; Inserm, U1011, F-59000, Lille, France; European Genomic Institute for Diabetes (EGID), FR3508, Lille, France; Institut Pasteur de Lille, F-59019, Lille, France.
Réjane
R
Paumelle
University of Lille, F-59000, Lille, France; Inserm, U1011, F-59000, Lille, France; European Genomic Institute for Diabetes (EGID), FR3508, Lille, France; Institut Pasteur de Lille, F-59019, Lille, France. Electronic address: bart.staels@pasteur-lille.fr.
Bart
B
Staels
D000818:Animals; D002899:Chromosomes, Human, Pair 9; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics* / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020641:Polymorphism, Single Nucleotide
C493966:CDKN2B protein, human; C417743:Cdkn2a protein, mouse; C493968:Cdkn2b protein, mouse; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16
ANRIL; CDKN2A; CDKN2B; GWAS; cardiovascular disease; type 2 diabetes