Critical Care: Genetic variant predicts poor response to bypass surgery

A variant of the gene for the inflammatory modulator interleukin (IL)-18 has been found to be associated with a prolonged ICU stay after cardiopulmonary bypass surgery. The study, published online in January in BioMed Central's journal Critical Care, links the TT genotype of the IL-18 9545 T/G polymorphism with a larger pro-inflammatory response.

David M. Shaw, MD, and colleagues from the University of British Columbia in Vancouver, Canada, investigated associations between the IL-18 haplotype and post-surgery inflammatory phenotype in 658 patients undergoing cardiopulmonary bypass surgery.

“Inflammatory gene polymorphisms have been linked to the intensity of the post-operative inflammatory response and to clinical outcomes after CPB surgery. Here, we've found an IL-18 variant that is associated with increased IL-18 levels and adverse outcomes,” said study author Keith R. Walley, MD, professor at the University of British Columbia and associate director at McDonald Research Laboratories in Vancouver, Canada.

The authors noted that IL-18 is known to increase levels of the pro-inflammatory cytokine TNF, while reducing levels of the anti-inflammatory IL-10. The TT genotype of the IL-18 9545 T/G polymorphism is believed by the authors to cause an increase in expression of IL-18.

Their research confirmed this mechanism and, according to Walley, “the resulting inflammatory response may account for the adverse clinical outcomes associated with the TT genotype post-surgery.”

In the cohort studied, the authors concluded that TT genotype was carried by 58 percent of the subjects, 34 percent were GT and 8 percent were GG. Apart from a small difference in body mass index, there were no significant differences in baseline characteristics between the groups.