title: Genetic mechanisms mediating atherosclerosis susceptibility at the chromosome 9p21 locus.
abstract: Recent genome-wide association studies have demonstrated that common genetic variants in a region of chromosome 9p21 confer risk of coronary artery disease (CAD) and other atherosclerotic conditions. Although the absolute increase in risk is small (some 20-30% increase in risk of CAD per copy of the deleterious alleles), the common occurrence of the variants means that their effect on the population risk of disease is estimated to be substantial. Studies investigating the relationship between risk variants and both "classical" and "emerging" atherosclerotic risk factors have found no evidence of association. This suggests that the effect of the 9p21 locus on atherosclerotic risk is mediated via a hitherto unknown pathway potentially amenable to therapeutic modulation. Investigation of potential disease mechanisms at this locus is therefore a focus of intense interest. In this review, we discuss the progress that has been made in the study of mechanisms and highlight the outstanding research questions.
authors.affiliation: Institute of Human Genetics, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK. mikecunnington@doctors.org.uk
authors.forename: Michael S
authors.initials: MS
authors.lastname: Cunnington
authors.forename: Bernard
authors.initials: B
authors.lastname: Keavney
mesh_terms: D000483:Alleles; D000818:Animals; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D002899:Chromosomes, Human, Pair 9 / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16