Review

Bench-to-bedside review: Association of genetic variation with sepsis

Ainsley M Sutherland¹ and Keith R Walley²

¹Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

²Critical Care Research Laboratories, Heart + Lung Institute, University of British Columbia, Burrard Street, Vancouver, British Columbia, Canada V6Z 1Y6

author email corresponding author email

Critical Care 2009, 13:210doi:10.1186/cc7702

Published:	29 April 2009

Abstract

Susceptibility and response to infectious disease is, in part, heritable. Initial attempts to identify the causal genetic polymorphisms have not been entirely successful because of the complexity of the genetic, epigenetic, and environmental factors that influence susceptibility and response to infectious disease and because of flaws in study design. Potential associations between clinical outcome from sepsis and many inflammatory cytokine gene polymorphisms, innate immunity pathway gene polymorphisms, and coagulation cascade polymorphisms have been observed. Confirmation in large, well conducted, multicenter studies is required to confirm current findings and to make them clinically applicable. Unbiased investigation of all genes in the human genome is an emerging approach. New, economical, high-throughput technologies may make this possible. It is now feasible to genotype thousands of tag single nucleotide polymorphisms across the genome in thousands of patients, thus addressing the issues of small sample size and bias in selecting candidate polymorphisms and genes for genetic association studies. By performing genome-wide association studies, genome-wide scans of nonsynonymous single nucleotide polymorphisms, and testing for differential allelic expression and copy number polymorphisms, we may yet be able to tease out the complex influence of genetic variation on susceptibility and response to infectious disease.