TY - JOUR
T1 - Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis
T2 - A study of cohorts from the Gambia, Guinea-Bissau, United States and Argentina
AU - Morris, Gerard A J
AU - Edwards, Digna R Velez
AU - Hill, Philip C.
AU - Wejse, Christian
AU - Bisseye, Cyrille
AU - Olesen, Rikke
AU - Edwards, Todd L.
AU - Gilbert, John R.
AU - Myers, Jamie L.
AU - Stryjewski, Martin E.
AU - Abbate, Eduardo
AU - Estevan, Rosa
AU - Hamilton, Carol D.
AU - Tacconelli, Alessandra
AU - Novelli, Giuseppe
AU - Brunetti, Ercole
AU - Aaby, Peter
AU - Sodemann, Morten
AU - Østergaard, Lars
AU - Adegbola, Richard
AU - Williams, Scott M.
AU - Scott, William K.
AU - Sirugo, Giorgio
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0016656
DO - 10.1371/journal.pone.0016656
M3 - Article
C2 - 21339808
AN - SCOPUS:79951806034
VL - 6
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 2
M1 - e16656
ER -