Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa.
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.
Tosh
Kerrie
K
*Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
Campbell
Sarah J
SJ
*Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
Fielding
Katherine
K
London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
Sillah
Jackson
J
Medical Research Council Laboratories, Fajara, The Gambia.
Bah
Boubacar
B
Programme National de Lutte Anti-Tuberculeuse, BP 634, Conakry, Republic of Guinea.
Gustafson
Per
P
Projecto de Saude Bandim, Danish Epidemiology Service Centre, Statens Serum Institut, Bissau, Guinea.
Manneh
Kebba
K
National Tuberculosis/Leprosy Control Programme, Banjul, The Gambia.
Lisse
Ida
I
Projecto de Saude Bandim, Danish Epidemiology Service Centre, Statens Serum Institut, Bissau, Guinea.
Sirugo
Giorgio
G
Medical Research Council Laboratories, Fajara, The Gambia.
Bennett
Steve
S
London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
Aaby
Peter
P
Projecto de Saude Bandim, Danish Epidemiology Service Centre, Statens Serum Institut, Bissau, Guinea.
McAdam
Keith P W J
KPWJ
London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
Bah-Sow
Oumou
O
Programme National de Lutte Anti-Tuberculeuse, BP 634, Conakry, Republic of Guinea.
Lienhardt
Christian
C
Medical Research Council Laboratories, Fajara, The Gambia.|Institut de Recherche pour le Développement, Route des Peres Maristes, Hann, BP1386, Dakar, Senegal; and.
Kramnik
Igor
I
Department of Immunology and Infectious Diseases, Harvard School of Public Health, 667 Huntington Avenue, Boston, MA 02115.
Hill
Adrian V S
AVS
*Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, United Kingdom; adrian.hill@imm.ox.ac.uk.
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
D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C412425:Sp110 protein, human