title: Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa.
abstract: The sst1 locus has been identified in a mouse model to control resistance and susceptibility of Mycobacterium tuberculosis infection. Subsequent studies have now identified Ipr1 (intracellular pathogen resistance 1) to be the gene responsible. Ipr1 is encoded within the sst1 locus and is expressed in the tuberculosis lung lesions and macrophages of sst1-resistant, but not sst1-susceptible mice. We have therefore examined the closest human homologue of Ipr1, SP110, for its ability to control susceptibility to M. tuberculosis infection in humans. In a study of families from The Gambia we have identified three polymorphisms that are associated with disease. On examination of additional families from Guinea-Bissau and the Republic of Guinea, two of these associations were independently replicated. These variants are in strong linkage disequilibrium with each other and lie within a 31-kb block of low haplotypic diversity, suggesting that a polymorphism within this region has a role in genetic susceptibility to tuberculosis in humans.
authors.affiliation: *Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
authors.forename: Kerrie
authors.initials: K
authors.lastname: Tosh
authors.affiliation: *Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Campbell
authors.affiliation: London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
authors.forename: Katherine
authors.initials: K
authors.lastname: Fielding
authors.affiliation: Medical Research Council Laboratories, Fajara, The Gambia.
authors.forename: Jackson
authors.initials: J
authors.lastname: Sillah
authors.affiliation: Programme National de Lutte Anti-Tuberculeuse, BP 634, Conakry, Republic of Guinea.
authors.forename: Boubacar
authors.initials: B
authors.lastname: Bah
authors.affiliation: Projecto de Saude Bandim, Danish Epidemiology Service Centre, Statens Serum Institut, Bissau, Guinea.
authors.forename: Per
authors.initials: P
authors.lastname: Gustafson
authors.affiliation: National Tuberculosis/Leprosy Control Programme, Banjul, The Gambia.
authors.forename: Kebba
authors.initials: K
authors.lastname: Manneh
authors.affiliation: Projecto de Saude Bandim, Danish Epidemiology Service Centre, Statens Serum Institut, Bissau, Guinea.
authors.forename: Ida
authors.initials: I
authors.lastname: Lisse
authors.affiliation: Medical Research Council Laboratories, Fajara, The Gambia.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sirugo
authors.affiliation: London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
authors.forename: Steve
authors.initials: S
authors.lastname: Bennett
authors.affiliation: Projecto de Saude Bandim, Danish Epidemiology Service Centre, Statens Serum Institut, Bissau, Guinea.
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.affiliation: London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
authors.forename: Keith P W J
authors.initials: KPWJ
authors.lastname: McAdam
authors.affiliation: Programme National de Lutte Anti-Tuberculeuse, BP 634, Conakry, Republic of Guinea.
authors.forename: Oumou
authors.initials: O
authors.lastname: Bah-Sow
authors.affiliation: Medical Research Council Laboratories, Fajara, The Gambia.|Institut de Recherche pour le Développement, Route des Peres Maristes, Hann, BP1386, Dakar, Senegal; and.
authors.forename: Christian
authors.initials: C
authors.lastname: Lienhardt
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 667 Huntington Avenue, Boston, MA 02115.
authors.forename: Igor
authors.initials: I
authors.lastname: Kramnik
authors.affiliation: *Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom; adrian.hill@imm.ox.ac.uk.
authors.forename: Adrian V S
authors.initials: AVS
authors.lastname: Hill
mesh_terms: D000349:Africa / Q000453:epidemiology; D018562:Disease Transmission, Infectious; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015778:Minor Histocompatibility Antigens; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics*; D014376:Tuberculosis / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology / Q000473:pathology
chemical_list: D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C412425:Sp110 protein, human