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

Autor: 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
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: PLoS ONE, Vol 6, Iss 2, p e16656 (2011)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0016656
Popis: 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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