Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West Africa

被引:90
作者
Tosh, Kerrie
Campbell, Sarah J.
Fielding, Katherine
Sillah, Jackson
Bah, Boubacar
Gustafson, Per
Manneh, Kebba
Lisse, Ida
Sirugo, Giorgio
Bennett, Steve
Aaby, Peter
McAdam, Keith P. W. J.
Bah-Sow, Oumou
Lienhardt, Christian
Kramnik, Igor
Hill, Adrian V. S.
机构
[1] Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England
[2] London Sch Hyg & Trop Med, London WC1E 7HT, England
[3] MRC Labs, Fajara, Gambia
[4] Programme Natl Lutte Anti TB, Conakry, Guinea
[5] Statens Serum Inst, Projecto Saude Bandim, Danish Epidemiol Serv Ctr, Bissau, Guinea Bissau
[6] Natl TB Leprosy Control Program, Banjul, Gambia
[7] Inst Rech Dev, Dakar, Senegal
[8] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA
基金
英国惠康基金;
关键词
association study; murine genetics; macrophage; LINKAGE DISEQUILIBRIUM; INTERFERON-GAMMA; RISK-FACTORS; TECHNOLOGY; RESISTANCE; INFECTION; IMMUNITY; RECEPTOR;
D O I
10.1073/pnas.0603340103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:10364 / 10368
页数:5
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