Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions

  • Fumagalli M
  • Pozzoli U
  • Cagliani R
 et al. 
  • 204

    Readers

    Mendeley users who have this article in their library.
  • 154

    Citations

    Citations of this article.

Abstract

Many human genes have adapted to the constant threat of exposure to infectious agents; according to the "hygiene hypothesis," lack of exposure to parasites in modern settings results in immune imbalances, augmenting susceptibility to the development of autoimmune and allergic conditions. Here, by estimating the number of pathogen species/genera in a specific geographic location (pathogen richness) for 52 human populations and analyzing 91 interleukin (IL)/IL receptor genes (IL genes), we show that helminths have been a major selective force on a subset of these genes. A population genetics analysis revealed that five IL genes, including IL7R and IL18RAP, have been a target of balancing selection, a selection process that maintains genetic variability within a population. Previous identification of polymorphisms in some of these loci, and their association with autoimmune conditions, prompted us to investigate the relationship between adaptation and disease. By searching for variants in IL genes identified in genome-wide association studies, we verified that six risk alleles for inflammatory bowel (IBD) or celiac disease are significantly correlated with micropathogen richness. These data support the hygiene hypothesis for IBD and provide a large set of putative targets for susceptibility to helminth infections.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Matteo Fumagalli

  • Uberto Pozzoli

  • Rachele Cagliani

  • Giacomo P. Comi

  • Stefania Riva

  • Mario Clerici

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free