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 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 AdegbolaScott M. Williams, William K Scott, Giorgio Sirugo

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Abstract

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
Article numbere16656
JournalPLoS One
Volume6
Issue number2
DOIs
StatePublished - Feb 24 2011

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Guinea-Bissau
Interleukin-12 Subunit p40
Gambia
Argentina
interleukins
cohort studies
Pulmonary Tuberculosis
tuberculosis
Cohort Studies
African Americans
Polymorphism
lungs
genetic variation
genetic polymorphism
Single Nucleotide Polymorphism
ancestry
Genes
interleukin-3
Population
South America

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis : A study of cohorts from the Gambia, Guinea-Bissau, United States and Argentina. / Morris, Gerard A J; Edwards, Digna R Velez; Hill, Philip C.; Wejse, Christian; Bisseye, Cyrille; Olesen, Rikke; Edwards, Todd L.; Gilbert, John; Myers, Jamie L.; Stryjewski, Martin E.; Abbate, Eduardo; Estevan, Rosa; Hamilton, Carol D.; Tacconelli, Alessandra; Novelli, Giuseppe; Brunetti, Ercole; Aaby, Peter; Sodemann, Morten; Østergaard, Lars; Adegbola, Richard; Williams, Scott M.; Scott, William K; Sirugo, Giorgio.

In: PLoS One, Vol. 6, No. 2, e16656, 24.02.2011.

Research output: Contribution to journalArticle

Morris, GAJ, Edwards, DRV, Hill, PC, Wejse, C, Bisseye, C, Olesen, R, Edwards, TL, Gilbert, J, Myers, JL, Stryjewski, ME, Abbate, E, Estevan, R, Hamilton, CD, Tacconelli, A, Novelli, G, Brunetti, E, Aaby, P, Sodemann, M, Østergaard, L, Adegbola, R, Williams, SM, Scott, WK & Sirugo, G 2011, 'Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis: A study of cohorts from the Gambia, Guinea-Bissau, United States and Argentina', PLoS One, vol. 6, no. 2, e16656. https://doi.org/10.1371/journal.pone.0016656
Morris, Gerard A J ; Edwards, Digna R Velez ; Hill, Philip C. ; Wejse, Christian ; Bisseye, Cyrille ; Olesen, Rikke ; Edwards, Todd L. ; Gilbert, John ; Myers, Jamie L. ; Stryjewski, Martin E. ; Abbate, Eduardo ; Estevan, Rosa ; Hamilton, Carol D. ; Tacconelli, Alessandra ; Novelli, Giuseppe ; Brunetti, Ercole ; Aaby, Peter ; Sodemann, Morten ; Østergaard, Lars ; Adegbola, Richard ; Williams, Scott M. ; Scott, William K ; Sirugo, Giorgio. / Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis : A study of cohorts from the Gambia, Guinea-Bissau, United States and Argentina. In: PLoS One. 2011 ; Vol. 6, No. 2.
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abstract = "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.",
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