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PEGASUS Research Projects
Perioperative Myocardial Infarction
7-15% of patients undergoing coronary bypass surgery will suffer from a subsequent PMI, despite the substantial advances in surgical, cardioprotective and anesthetic techniques. In a recent study, PEGASUS investigators found that patients with 6 specific polymorphisms involved in the body’s immune response are significantly more likely to suffer damage of heart tissues after cardiac surgery. Of the 6 polymorphisms, 4 are directly associated with the damage while the other 2 polymorphisms are found in genes that would normally have a protective effect.
The investigators identified 48 known polymorphisms of 23 candidate genes that are all involved with the body's immune response. 434 patients undergoing coronary bypass surgery were enrolled and blood samples were taken 24 hours after surgery. 12% of the patients (52 total) were considered to have suffered an MI. Investigators determined this by looking at the patients CK-MB levels. If the levels were at least ten times higher than the upper limit of normal, they were considered to have suffered a post-operative MI.
Investigators then looked for genetic differences between the patients who suffered post-operative MI and those who did not using a two-step genetic analysis. It was found that looking at the polymorphisms individually only had a modest effect, but had a significant effect when combining them.
Specifically, the deleterious polymorphisms were in genes that code for the production of four different proteins: interleukin-6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM1) and lipopolysaccharide-binding protein (LBP).
The last polymorphism – in a gene that codes for the enzyme catalase – appears to be involved in mediating the effects of oxidative stress. The normal version of the gene produces proteins that can blunt the negative effects of oxygen free radicals, while the polymorphism is unable to do so effectively. It is well established that heart muscle cells are placed under oxidative stress during reperfusion.
Mangano DT et al, JAMA 1997;277:325-32
Force T et al, Circulation 1990;82:903-12
Podgoreanu MV et al., Circulation 2006; 114(Suppl 1):275-281
| IL6 -572G/C (rs1800796) |
OR 2.4 (1.02-5.9, p=0.007) |
| ICAM1 K469E (rs5498) |
OR 1.8 (1.1-2.8, p=0.01) |
| CRP 1846C/T (rs1205) |
OR 2.4 (1.1-5.1, p=0.02) |
| LBP 326T/C (rs2232582) |
OR 2.5 (1.2-2.8, p=0.02) |
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| CAT -844T/C (rs769214) |
OR 0.5 (0.3-0.8, p=0.01) |
| SELE 98G/T (rs1805193) |
OR 0.1 (0.02-0.9, 0.03) |
Podgoreanu MV et al., Circulation 2006; 114(Suppl 1):275-281
Podgoreanu MV et al., Circulation 2006; 114(Suppl 1):275-281
Genetic Variants Protective Against PMI
Podgoreanu MV et al., Circulation 2006; 114(Suppl 1):275-281
Only 3 SNPs were significant after controlling FDR <10%
Podgoreanu MV et al., Circulation 2006; 114(Suppl 1):275-281
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