Influence of genotype on perioperative risk and outcome

Abstract

Rapid progress in molecular biology has revolutionized our ability to assess the impact of genetic variability on disease characterization and outcome. Despite these encouraging results, a few words of caution are warranted for the clinician trying to critically evaluate the increasingly large body of literature linking various allotypes to specific, adverse outcomes. First, it is important to recognize that gene association studies do not imply causality. The identified genotype may actually be clinically "silent" but be linked to one or more other allotypes that individually or collectively form a disease haplotype. Second, because gene association studies typically involve multiple comparisons of many variables within different populations, there is always the potential for the identification of spurious gene associations that may or may not prove significant or causal. Third, one cannot extrapolate positive gene association findings to other populations with different genetic backgrounds. Finally, it is important to recognize that environmental factors may influence gene association findings even in individuals of homogenous genetic backgrounds. For example, clinically significant polymorphisms in gene promotor regions influenced by the induction of CPB might otherwise go unrecognized in patients having off-pump cardiac surgery. Thus, at present, a strong need remains for prospective, sufficiently powered, gene association studies conducted in well-defined, highly phenotyped populations. Only then can we begin to critically evaluate the relative importance or clinical significance of various gene associations. Continued identification of allotypes and haplotypes predictive of adverse perioperative events may not only further our understanding of the pathophysiologic response to surgery but also potentially decrease surgical morbidity and mortality via preoperative risk assessment and the administration of prophylactic therapy.