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

Abstract of an article published in The Journal of Experimental Medicine, Vol. 206, No. 6, 1395-1408

Matteo Fumagalli1,2, Uberto Pozzoli1, Rachele Cagliani1, Giacomo P. Comi3, Stefania Riva1, Mario Clerici4,5, Nereo Bresolin1,3, and Manuela Sironi1
1 Scientific Institute IRCCS E. Medea, Bioinformatic Laboratory, 23842 Bosisio Parini, Italy
2 Bioengineering Department, Politecnico di Milano, 20133 Milan, Italy
3 Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena Foundation, 20100 Milan, Italy
4 Department of Biomedical Sciences and Technologies LITA Segrate, University of Milan, 20090 Milan, Italy
5 Laboratory of Molecular Medicine and Biotechnology, Don C. Gnocchi ONLUS Foundation IRCCS, 20148 Milan, Italy


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.

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First Published in 2009

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