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

Morris GA, Edwards DR, Hill PC, Wejse C, Bisseye C, Olesen R, Edwards TL, Gilbert JR, 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
PLoS One. 2011 6 (2): e16656

PMID: 21339808 · PMCID: PMC3037276 · DOI:10.1371/journal.pone.0016656

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.

MeSH Terms (24)

Adolescent Adult African Continental Ancestry Group Aged Aged, 80 and over Argentina Case-Control Studies Cohort Studies Female Gambia Gene Frequency Genetic Association Studies Genetics, Population Genetic Variation Guinea-Bissau Humans Interleukin-12 Subunit p40 Linkage Disequilibrium Male Middle Aged Polymorphism, Single Nucleotide Tuberculosis, Pulmonary United States Young Adult

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