title: Parasites represent a major selective force for interleukin genes and shape the genetic predisposition to autoimmune conditions.
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.
authors.affiliation: Scientific Institute IRCCS E. Medea, Bioinformatic Laboratory, 23842 Bosisio Parini, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fumagalli
authors.forename: Uberto
authors.initials: U
authors.lastname: Pozzoli
authors.forename: Rachele
authors.initials: R
authors.lastname: Cagliani
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.forename: Stefania
authors.initials: S
authors.lastname: Riva
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Manuela
authors.initials: M
authors.lastname: Sironi
mesh_terms: D000483:Alleles; D000818:Animals; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005828:Genetics, Population; D006239:Haplotypes; D006376:Helminths / Q000145:classification / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics* / Q000276:immunology; D012641:Selection, Genetic
chemical_list: D007378:Interleukins; D018123:Receptors, Interleukin