Functional Genomics of the Oxidative Stress Pathway

Oxidative stress plays an important role in the pathogenesis of a variety of disorders including cardiovascular disease. Understanding the genetic background of increased oxidative stress will facilitate targeted prevention and therapy of these diseases. Strategies to analyse genomics of oxidative stress include genome scans in rodent models, construction of congenic animals and candidate gene approaches. A new family of candidate genes for human cardiovascular disease, glutathione S-transferases (GSTMs), have been derived from experiments in congenic rats. Knowledge of the physiology of superoxide production led to analysis of genetic variants of the CYBA gene encoding the p22phox unit of NADPH oxidase. Against the background of rapidly evolving genotyping technology we are currently facing challenges in accurate phenotyping and biomarker development to measure oxidative stress, together with the need to develop new statistical paradigms to encompass gene-gene and gene-environment interactions.