deCODE MI™

Analyzes five SNPs in the CYP2C19 gene that affect response to the anti-platelet drug clopidogrel. This test identifies those who may need adjustment of their clopidogrel dose or who should be put on an alternative medicaiton to prevent recurrent adverse cardiovascular events.

Screening and prevention

How deCODE MI™ can help.

More Comprehensive Risk Assessment

Understanding a patient’s risk of cardiovascular disease is the prerequisite for effective prevention, including decisions and follow-through on life style modification and medication. deCODE MI™ detects genetic risk factors for heart attack that are independent of traditional risk factors, helping to provide a more complete picture of individual susceptibility as well as important information on risk of early-onset disease.

Integration with established risk modelling tools

The results of deCODE MI™ are presented as a numerical score of individual risk of heart attack compared to the population average. Because this risk is complementary to that conferred by traditional risk factors, deCODE MI™ results can be used directly to modify scores from the Framingham, Reynolds, or ARIC tools. This can impact the recommended prevention strategies and medication for a substantial proportion of patients.

Empowering physicians and patients

Preventive measures for MI are to a great extent dependent on successful changes in lifestyle. deCODE MI™ results can give physicians’ advice extra emphasis and impact, and provide their patients with additional incentive to follow through on that advice.

The deCODE MI™ risk variants are the first widely-replicated, common genetic variants ever found to associate with substantially increased risk of coronary heart disease and MI as public health problems.

The association of the eight markers used in the deCODE MI™ test to the risk for MI has been validated in multiple independent populations, covering thousands of people (table). Of most impact and highest significance is the chromosome 9p21 marker discovered by deCODE and published in Science in June 2007⁽⁵⁾. Some 20-22% of people of European descent have been shown to carry two copies of the risk variants. Having two copies of this risk variant alone has been shown to correspond to an approximately 60% increase in likelihood of early onset MI compared to the population average and a 30% increase in risk of MI regardless of age of onset.

The risk variants tested for by deCODE’s MI test at the 9p21 locus are the “G” allele of SNP rs10757278 and the “C” allele in SNP rs1333049 located in the vicinity of the tumor suppressor genes CDKN2A and CDKN2B. These genes encode proteins called p16INK4a, ARF, and p15INK4b that play a critical role in regulating cell proliferation, cell aging and senescence, as well as apoptosis in many cell types. These are all important features of atherogenesis, the underlying cause of coronary heart disease and MI. Despite their vicinity to these genes, the precise mechanism through which the genetic variants affect the pathogenesis of MI, and whether that effect is through the protein products of CDKN2A and CDKN2B, remains to be elucidated.

The other 7 SNPs of the deCODE MI™ test were also discovered and verified by deCODE and others in multiple populations of European descent and their frequencies and risk effect compared to the 9p21 marker can be seen in this table.

Chromosome	SNP	Non-risk allele homozygosity population frequency relative risk	Heterozygosity population frequency relative risk	Risk allele homozygosity population frequency relative risk	Number of cases/controls in studies	Number of independent sample sets studied	References
9p21.3	rs10757278	AA 23% 0.76	AG 50% 0.98	GG 27% 1.25	4587 / 12767	4	5-12
12q24.12	rs3184504	CC 30% 0.89	CT 49% 1.00	TT 20% 1.14	6650 / 40621	8	13
3q22.3	rs9818870	CC 71% 0.95	CT 26% 1.10	TT 2.3% 1.26	19.407 / 21.366	12	14
1q41	rs17465637	AA 7.8% 0.82	AC 40% 0.94	CC 52% 1.07	12544 / 44118	17	15-18
10q11.21	rs1746048	TT 2.6% 0.76	TC 27% 0.89	CC 70% 1.05	12544 / 44118	17	15,19
6p24.1	rs12526453	GG 12.2% 0.86	GC 45% 0.96	CC 42% 1.08	12544 / 44118	17	15
2q33.1	rs6725887	TT 74% 0.95	TC 24% 1.12	CC 2% 1.3	12544 / 44118	17	15

Information on studies verifying the markers used in deCODE MI™ for East Asians can be seen in this table.

		deCODE MI™ SNP		Information used for risk estimation and validation of each SNP and relevant reference
Locus	Chr	SNP	Risk Allele / Other Allele	SNP	Risk Allele / Other Allele	Risk Allele OR	Freq. of risk allele in controls	Affected sample size	Control sample size	Number of independent sample sets	Reference	Additional supportive publications
CDKN2A / CDKN2b	9	rs2383207	G/A	rs2383207	G/A	1.32	0.647	611	294	1	6	7,8,12,20
BRAP	12	rs3782886	G/A	rs3782886	G/A	1.42	0.27	3686	4885	2	21	22

The deCODE MI™ test is performed using the llumina I-select BeadChip. This highly reliable method has a greater than 99.9% accuracy and is based on a proprietary Illumina technology using DNA amplification, hybridization and fluorescent detection.

This content was last reviewed on March 16, 2011.