|Cardiac Risk Prediction Array|
Simultaneous genotyping of 19 SNPs for a reliable CHD risk assessment
Coronary Heart Disease (CHD) is the leading cause of death in the developed world and its prevention is a core activity in general practice worldwide. For example, clinical guidelines from the Joint Cardiac Societies and NICE in the UK recommend that patients at greater than 20% risk of CHD in the next ten years should be classified as high risk and considered for intensive lifestyle intervention and lipid lowering therapy, primarily the prescription of statins.
Current CHD risk assessment tools based on common risk factors such as blood pressure and blood cholesterol levels have low predictive value and take no account of genetic predisposition to CHD. Cooper et al reported only 14% of CHD events during a ten year period were predicted by these algorithmic tools.
In recent years Genome Wide Association Studies (GWAS) have been carried out to identify genetic variants associated with CHD. This involves comparing millions of loci in the genomes of a population suffering from CHD and a control population. Meta-analysis of such studies has identified 18 variants (referred to as single nucleotide polymorphisms (SNPs)) as being associated with CHD. Individually, the presence of an ‘at risk’ variant does not greatly increase the risk of developing CHD. However, the presence of multiple ‘at risk’ alleles can increase the risk of developing CHD two-fold or greater, an effect similar to being a current smoker. Combining such genotype information with common risk factors could allow individuals to be more accurately classified and preventative therapies and lifestyle advice targeted to those who require it most.
The Cardiac Risk Prediction Array
In order to utilise the GWAS findings in a clinical setting, individuals require to be genotyped for each of the 18 CHD ‘at risk’ SNPs. At present this can be a time consuming and expensive process. Together with key opinion leaders in cardiovascular genetics, Randox has developed a rapid array which will allow all 18 SNPs to be genotyped simultaneously. Firstly, a multiplex PCR reaction is performed, where the products amplified correspond to the genotype of the patient sample. The PCR products are then hybridised onto the biochip array and imaged using the Evidence Investigator analyser to identify which PCR products are present. Thus a patient sample can be genotyped within one day. The genotype information is then put into an algorithm which weights each SNP and calculates a CHD genetic risk score. The CHD genetic risk score is combined with common risk factors and an overall CHD risk score is calculated.
Response to statin treatment
A further important SNP which can predict response to particular statin therapies has been included in the array. Individuals who are homozygous (frequency = 0.13) for the risk allele are 17 times more likely to suffer from statin-induced myopathy when treated with high doses of simvastatin. Identifying patients with a higher risk of suffering statin-induced myopathy would allow clinicians to make more informed decisions when prescribing lipid lowering therapies.
Benefits of the Cardiac Risk Prediction Array
To the patient:
To the laboratory