Interleukin-10, age and acute lung injury genetics: the action is in the interaction.

A cute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are important public health issues, and both incidence and mortality increase with age [1]. Given that only a moderate percentage of individuals with the same level of exposure develop ALI/ ARDS, it is logical to investigate whether inherent interindivid-ual variation will, in part, determine the risk of ALI/ARDS. Better understanding of the genetic factors influencing both risk of developing ALI/ARDS and outcomes following ALI/ ARDS may aid in the identification of high-risk individuals, suggest areas for laboratory research and lead to the development of more specific, targeted pharmacogenomic strategies for treatment and prevention [2]. Research on the genetic epidemiology of ALI/ARDS is in its early stages. Studies in this area have either used physiological hypotheses (including angiotensin-converting enzyme and surfactant proteins) [3, 4] or bioinformatics approaches based on animal experiments to select candidate genes [5]. In this issue of the European Respiratory Journal, GONG et al. [6] provide an important contribution to understanding the genetic aetiology of ARDS and outcomes following ARDS. In a well-constructed cohort study, the authors report an association of an interleukin (IL)-10 promoter polymorphism with ALI/ ARDS that differed by strata of age. GONG et al. [6] should be commended on several important strengths of their study. First, the large nested case–control design ensured that all non-ARDS subjects were drawn from the same at-risk cohort, minimising the bias due to selection of controls that can plague gene-association studies [7]. Secondly, rigorous methods for phenotyping ARDS were employed, thereby minimising misclassification. Thirdly, careful and rigorous statistical methods were used to test for interaction. The resultant findings highlight some important and current issues in genetic studies of ALI/ARDS aetiology and outcomes. First, the main finding regarding ALI risk is an interaction of IL-10 genotype with age. The epidemiological term ''interaction'' refers to the concept that the effect of a risk factor (IL-10 genotype) on the outcome (ALI/ARDS) may be modified by a third factor (in this case age) [8]. Interactions are important to genetic studies of complex diseases, particularly in the case of ALI/ARDS where there are many variables that may modify disease risk and outcomes, such as different precipitating factors and comorbid diseases. The study of interactions in epidemiological studies is usually exploratory, unless specified a priori and the study is appropriately powered to detect them. In the study by GONG et …