The landscape of human genes involved in the immune response to parasitic worms

BMC Evol Biol. 2010 Aug 31:10:264. doi: 10.1186/1471-2148-10-264.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Asthma / genetics
  • Genetic Predisposition to Disease
  • Helminths / classification
  • Helminths / immunology*
  • Humans
  • Hypersensitivity / genetics
  • Parasitic Diseases / genetics
  • Parasitic Diseases / immunology*
  • Parasitic Diseases / parasitology*
  • Polymorphism, Single Nucleotide / genetics