9p21 and the Genetic Revolution for Coronary Artery Disease

Abstract

BACKGROUND It has long been recognized that 50% of the susceptibility for coronary artery disease (CAD) is due to predisposing genetic factors. Comprehensive prevention is likely to require knowledge of these genetic factors. CONTENT Using a genomewide association study (GWAS), the Ottawa Heart Genomic Study and the deCODE group simultaneously identified the first genetic risk variant, at chromosome 9p21. The 9p21 variant became the first risk factor to be identified since 1964. 9p21 occurs in 75% of the population except for African Americans and is associated with a 25% increased risk for CAD with 1 copy and a 50% increased risk with 2 copies. Perhaps the most remarkable finding is that 9p21 is independent of all known risk factors, indicating there are factors contributing to the pathogenesis of CAD that are yet unknown. 9p21 in individuals with premature CAD is associated with a 2-fold increase in risk, similar to that of smoking and cholesterol. Routine genetic testing will probably remain controversial until a specific treatment is developed. Over a period of 5 years, however, GWASs have identified 30 genetic variants for CAD risk, of which only 6 act through the known risk factors. SUMMARY The 9p21 variant has now been established as an independent risk factor for CAD and, along with the additional 29 risk genetic variants recently identified, is likely to provide the thrust for genetic testing and personalized medicine in the near future.

Genetics and Genomics for the Prevention and Treatment of Cardiovascular Disease: Update

“…35 The pattern of pleiotropic associations suggests a hypothesis that cells responsible for maintaining the integrity of the arterial wall may mediate both atherosclerotic and nonatherosclerotic diseases. 363,364 Although this hypothesis is the leading hypothesis tying these observations at the population level together, it remains to be proven.…”

Association of Leukotriene Gene Variants and Plasma LTB4 Levels with Coronary Artery Disease in Asian Indians

“…In fact, the average MAF was considerably higher for SNPs in the noncoding regions (20%-25%) than in the coding regions (12%-16%) [30], making it difficult to pick them up in our rather small-sized cohort. A recent review of GWAS suggests that more than 70% of genetic variants identified to date for CAD are located in the noncoding regions [31].…”

Impact of Biomarkers, Proteomics, and Genomics in Cardiovascular Disease

“…This area addresses multiple topics, including cardiovascular sequencing, transcriptomics, and epigenetics (18 ); general genomics (19 ); 9p21 (20 ); metabolomics (21 ); and PCSK9 and LDL cholesterol responses from the JUPITER trial (22 ).…”