A customized genetic approach to the number one killer: coronary artery disease

作者：Roberts Robert^*

来源：Current Opinion in Cardiology, 2008, 23(6): 629-633.

DOI：10.1097/HCO.0b013e32830c9254

• 9p21 variant
• coronary artery disease
• genetic susceptibility
• risk variant
• single nucleotide polymorphisms

Purpose of review
To review the evidence supporting genetic predisposition to coronary artery disease (CAD). Secondly, to elucidate the barriers precluding the identification of genes responsible for CAD. Thirdly, to indicate the new technology now available to overcome these barriers and summarize current progress.
Recent findings
Evidence strongly supports that 50% of susceptibility to CAD is genetic. Prevention of CAD requires comprehensive genetic and risk factor modification. Technology to perform genome-wide association studies became available in 2005, namely, the microarrays with 500 000 and 1 million single nucleotide polymorphisms as DNA markers for high-throughput genotyping to determine gene frequencies in large datasets of cases and controls. The first genetic variant, 9p21, for CAD was identified in the Ottawa Heart Genomic study. This is not only a genetic risk factor but also independent of other known risk factors for CAD. 9p21 was subsequently confirmed as a risk variant in several other independent studies involving 64 000 Caucasians. 9p21 increases the risk of CAD by 40% and 20% in heterozygous or homozygous forms respectively. It occurs in 75% of Caucasians, and has recently been confirmed in several other ethnic groups.
Summary
Thus, identification of predisposition to CAD is well underway with genome-wide association studies and the first common genetic risk variant, 9p21, has been identified.

• 出版日期2008-11