Lars Jørgen Østergaard

Interleukin 12B (IL12B) Genetic Variation and Pulmonary Tuberculosis: A Study of Cohorts from The Gambia, Guinea-Bissau, United States and Argentina

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Gerard A J Morris
  • ,
  • Digna R Velez Edwards, Denmark
  • Philip C Hill
  • ,
  • Christian Wejse
  • Cyrille Bisseye
  • ,
  • Rikke Olesen
  • Todd L Edwards, Denmark
  • John R Gilbert
  • ,
  • Jamie L Myers
  • ,
  • Martin E Stryjewski
  • ,
  • Eduardo Abbate
  • ,
  • Rosa Estevan
  • ,
  • Carol D Hamilton, Denmark
  • Alessandra Tacconelli
  • ,
  • Giuseppe Novelli
  • ,
  • Ercole Brunetti
  • ,
  • Peter Aaby
  • ,
  • Morten Sodemann
  • ,
  • Lars Jørgen Østergaard
  • Richard Adegbola
  • ,
  • Scott M Williams, Denmark
  • William K Scott, Denmark
  • Giorgio Sirugo
  • The Department of Infectious Diseases
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.
Original languageEnglish
JournalP L o S One
Volume6
Issue2
Pages (from-to)e16656
ISSN1932-6203
DOIs
Publication statusPublished - 1 Jan 2011

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