title: Human genetic susceptibility to intracellular pathogens.
abstract: Intracellular pathogens contribute to a significant proportion of infectious disease morbidity and mortality worldwide. Increasing evidence points to a major role for host genetics in explaining inter-individual variation in susceptibility to infectious diseases. A number of monogenic disorders predisposing to infectious disease have been reported, including susceptibility to intracellular pathogens in association with mutations in genes of the interleukin-12/interleukin-23/interferon-γ axis. Common genetic variants have also been demonstrated to regulate susceptibility to intracellular infection, for example the CCR5Δ32 polymorphism that modulates human immunodeficiency virus-1 (HIV-1) disease progression. Genome-wide association study approaches are being increasingly utilized to define genetic variants underlying susceptibility to major infectious diseases. This review focuses on the current state-of-the-art in genetics and genomics as pertains to understanding the genetic contribution to human susceptibility to infectious diseases caused by intracellular pathogens such as tuberculosis, leprosy, HIV-1, hepatitis, and malaria, with a particular emphasis on insights from recent genome-wide approaches. The results from these studies implicate common genetic variants in novel molecular pathways involved in human immunity to specific pathogens.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Fredrik O
authors.initials: FO
authors.lastname: Vannberg
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chapman
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D003141:Communicable Diseases / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000235:genetics; D006505:Hepatitis / Q000235:genetics; D006801:Humans; D007918:Leprosy / Q000235:genetics; D008288:Malaria / Q000235:genetics; D014376:Tuberculosis / Q000235:genetics; D014777:Virus Diseases / Q000235:genetics