@article{fdi:010066740,
  title = {{A} locus at 5q33.3 confers resistance to tuberculosis in highly susceptible individuals},
  author = {{S}obota, {R}. {S}. and {S}tein, {C}. {M}. and {K}odaman, {N}. and {S}cheinfeldt, {L}. {B}. and {M}aro, {I}. and {W}ieland-{A}lter, {W}. and {I}go, {R}. {P}. and {M}agohe, {A}. and {M}alone, {L}. {L}. and {C}hervenak, {K}. and {H}all, {N}. {B}. and {M}odongo, {C}. and {Z}etola, {N}. and {M}atee, {M}. and {J}oloba, {M}. and {F}roment, {A}lain and {N}yambo, {T}. {B}. and {M}oore, {J}. {H}. and {S}cott, {W}. {K}. and {L}ahey, {T}. and {B}oom, {W}. {H}. and von {R}eyn, {C}. {F}. and {T}ishkoff, {S}. {A}. and {S}irugo, {G}. and {W}illiams, {S}. {M}.},
  editor = {},
  language = {{ENG}},
  abstract = {{I}mmunosuppression resulting from {HIV} infection increases the risk of progression to active tuberculosis ({TB}) both in individuals newly exposed to {M}ycobacterium tuberculosis ({MTB}) and in those with latent infections. {W}e hypothesized that {HIV}-positive individuals who do not develop {TB}, despite living in areas where it is hyperendemic, provide a model of natural resistance. {W}e performed a genome-wide association study of {TB} resistance by using 581 {HIV}-positive {U}gandans and {T}anzanians enrolled in prospective cohort studies of {TB}; 267 of these individuals developed active {TB}, and 314 did not. {A} common variant, rs4921437 at 5q33.3, was significantly associated with {TB} (odds ratio = 0.37, p = 2.11 x 10(-8)). {T}his variant lies within a genomic region that includes {IL}12{B} and is embedded in an {H}3{K}27{A}c histone mark. {T}he locus also displays consistent patterns of linkage disequilibrium across {A}frican populations and has signals of strong selection in populations from equatorial {A}frica. {A}long with prior studies demonstrating that therapy with {IL}-12 (the cytokine encoded in part by {IL}12{B}, associated with longer survival following {MTB} infection in mice deficient in {CD}4 {T} cells), our results suggest that this pathway might be an excellent target for the development of new modalities for treating {TB}, especially for {HIV}-positive individuals. {O}ur results also indicate that studying extreme disease resistance in the face of extensive exposure can increase the power to detect associations in complex infectious disease.},
  keywords = {{TANZANIE} ; {OUGANDA}},
  booktitle = {},
  journal = {{A}merican {J}ournal of {H}uman {G}enetics},
  volume = {98},
  numero = {3},
  pages = {514--524},
  ISSN = {0002-9297},
  year = {2016},
  DOI = {10.1016/j.ajhg.2016.01.015},
  URL = {https://www.documentation.ird.fr/hor/fdi:010066740},
}