Can the Preoperative Assessment of Genetic Polymorphisms for Cytokines Reliably Predict Clinical Events Induced by the Post-Cardiopulmonary Bypass Inflammatory Response?

Background: The inflammatory response induced by cardiopulmonary bypass (CPB) is still accountable for severe post-operative complications. Recent genetic studies have assessed the individual implication of single nucleotide polymorphisms (SNPs) of cytokines and apolipoprotein E in the magnitude of this response but the clinical relevance of these findings remains uncertain. We therefore studied the relationship between several SNPs, the corresponding cytokine circulating levels and postoperative clinical events in patients who underwent coronary artery bypass grafting (CABG) under CPB. Methods: We prospectively analyzed 126 consecutive patients referred for elective CABG. Patients were genotyped for SNPs of TNFβ ( Arg13Cys, +252A>G ), TNFα ( -308G>A ), IL6 ( -597A>G, −572G>C, −174G>C ), IL10 ( -592C>A, c*117C>T ), and apoE ( Cys112Arg, Arg158Cys ). Serum samples were retrieved at different perioperative time points to measure cytokine levels. The Primary Clinical Endpoint (PCE) was a composite of postoperative death, low cardiac output, myocardial infarction, acute respiratory distress syndrome, hepatic insufficiency, sepsis, or acute renal insufficiency. The Secondary Clinical Endpoint (SCE) extended PCE to include diuresis 2 /FiO 2 1L/24h. Results: In multivariate analysis, neither SNPs nor serum cytokine levels were predictive for PCE. Only patients homozygous for IL6-174GG were found to have a reduced incidence of the SCE (p=0.02) whereas this risk was higher for those carrying TNFβ+252 AA-AG (p Conclusions: Genomic determination of SNPs for cytokines predominantly involved in the postCPB inflammatory response seems to only have a limited predictive value of clinically relevant postoperative complications. Consequently this mode of screening is unlikely to really impact the perioperative management of patients undergoing on-pump CABG surgery.