PLoS ONE (Feb 2011)

Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis: a study of cohorts from The Gambia, Guinea-Bissau, United States and Argentina.

  • Gerard A J Morris,
  • Digna R Velez Edwards,
  • Philip C Hill,
  • Christian Wejse,
  • Cyrille Bisseye,
  • Rikke Olesen,
  • Todd L Edwards,
  • John R Gilbert,
  • Jamie L Myers,
  • Martin E Stryjewski,
  • Eduardo Abbate,
  • Rosa Estevan,
  • Carol D Hamilton,
  • Alessandra Tacconelli,
  • Giuseppe Novelli,
  • Ercole Brunetti,
  • Peter Aaby,
  • Morten Sodemann,
  • Lars Østergaard,
  • Richard Adegbola,
  • Scott M Williams,
  • William K Scott,
  • Giorgio Sirugo

DOI
https://doi.org/10.1371/journal.pone.0016656
Journal volume & issue
Vol. 6, no. 2
p. e16656

Abstract

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We examined whether polymorphisms in interleukin-12B (IL12B) associate with susceptibility to pulmonary tuberculosis (PTB) in two West African populations (from The Gambia and Guinea-Bissau) and in two independent populations from North and South America. Nine polymorphisms (seven SNPs, one insertion/deletion, one microsatellite) were analyzed in 321 PTB cases and 346 controls from Guinea-Bissau and 280 PTB cases and 286 controls from The Gambia. For replication we studied 281 case and 179 control African-American samples and 221 cases and 144 controls of European ancestry from the US and Argentina. First-stage single locus analyses revealed signals of association at IL12B 3' UTR SNP rs3212227 (unadjusted allelic p = 0.04; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61-0.99]) in Guinea-Bissau and rs11574790 (unadjusted allelic p = 0.05; additive genotypic p = 0.05, OR = 0.76, 95% CI [0.58-1.00]) in The Gambia. Association of rs3212227 was then replicated in African-Americans (rs3212227 allelic p = 0.002; additive genotypic p = 0.05, OR = 0.78, 95% CI [0.61-1.00]); most importantly, in the African-American cohort, multiple significant signals of association (seven of the nine polymorphisms tested) were detected throughout the gene. These data suggest that genetic variation in IL12B, a highly relevant candidate gene, is a risk factor for PTB in populations of African ancestry, although further studies will be required to confirm this association and identify the precise mechanism underlying it.