A Survey of Cytokine Expression Polymorphism in Human European Populations

Cytokines are soluble immunomodulatory glycoproteins involved in the regulation of processes associated with inflammation, immune response, and hemopoiesis. Changes in cytokine expression or activity can lead to alterations in these responses. Cytokines and their receptors are often encoded by highly polymorphic genes. In recent years, surveys using general continental-based samples have suggested differences in the distribution of cytokine genetic polymorphisms. Some genotypes are responsible for the observed interindividual differences in levels of cytokine production, and thereby constitute a mechanism for adaptive modulation of the immune response. Here, we report results of a survey of common polymorphisms giving differential expression in anti-inflammatory (TGFβ1 and IL-10) and pro-inflammatory (TNFα, IFNγ, and IL-6) cytokines in eighteen geographically distinct populations from Europe. Our preliminary analyses show that certain genotypes for specific cytokines document a non-random distribution suggesting significant regional variation. When the data are viewed from an evolutionary perspective focusing on the interplay between pro-inflammatory and anti-inflammatory cytokines constituting the inflammation phenotype, there appears to be a trend of decreased inflammation driven by selection.