The landscape of human genes involved in the immune response to parasitic worms.
BACKGROUND
More than 2 billion individuals worldwide suffer from helminth infections. The highest parasite burdens occur in children and helminth infection during pregnancy is a risk factor for preterm delivery and reduced birth weight. Therefore, helminth infections can be regarded as a strong selective pressure.


RESULTS
Here we propose that candidate susceptibility genes for parasitic worm infections can be identified by searching for SNPs that display a strong correlation with the diversity of helminth species/genera transmitted in different geographic areas. By a genome-wide search we identified 3478 variants that correlate with helminth diversity. These SNPs map to 810 distinct human genes including loci involved in regulatory T cell function and in macrophage activation, as well as leukocyte integrins and co-inhibitory molecules. Analysis of functional relationships among these genes identified complex interaction networks centred around Th2 cytokines. Finally, several genes carrying candidate targets for helminth-driven selective pressure also harbour susceptibility alleles for asthma/allergy or are involved in airway hyper-responsiveness, therefore expanding the known parallelism between these conditions and parasitic infections.


CONCLUSIONS
Our data provide a landscape of human genes that modulate susceptibility to helminths and indicate parasitic worms as one of the major selective forces in humans.
Fumagalli
Matteo
M
Scientific Institute IRCCS E, Medea, Bioinformatic Lab, Via don L, Monza 20, 23842 Bosisio, Parini, LC, Italy.
Pozzoli
Uberto
U
Cagliani
Rachele
R
Comi
Giacomo P
GP
Bresolin
Nereo
N
Clerici
Mario
M
Sironi
Manuela
M
D000483:Alleles; D000818:Animals; D001249:Asthma / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006376:Helminths / Q000145:classification / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics; D010272:Parasitic Diseases / Q000235:genetics / Q000276:immunology* / Q000469:parasitology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
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