title: Interleukin 12B (IL12B) genetic variation and pulmonary tuberculosis: a study of cohorts from The Gambia, Guinea-Bissau, United States and Argentina.
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.
authors.affiliation: MRC Laboratories, Fajara, The Gambia (West Africa).
authors.forename: Gerard A J
authors.initials: GA
authors.lastname: Morris
authors.forename: Digna R Velez
authors.initials: DR
authors.lastname: Edwards
authors.forename: Philip C
authors.initials: PC
authors.lastname: Hill
authors.forename: Christian
authors.initials: C
authors.lastname: Wejse
authors.forename: Cyrille
authors.initials: C
authors.lastname: Bisseye
authors.forename: Rikke
authors.initials: R
authors.lastname: Olesen
authors.forename: Todd L
authors.initials: TL
authors.lastname: Edwards
authors.forename: John R
authors.initials: JR
authors.lastname: Gilbert
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Myers
authors.forename: Martin E
authors.initials: ME
authors.lastname: Stryjewski
authors.forename: Eduardo
authors.initials: E
authors.lastname: Abbate
authors.forename: Rosa
authors.initials: R
authors.lastname: Estevan
authors.forename: Carol D
authors.initials: CD
authors.lastname: Hamilton
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tacconelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
authors.forename: Ercole
authors.initials: E
authors.lastname: Brunetti
authors.forename: Peter
authors.initials: P
authors.lastname: Aaby
authors.forename: Morten
authors.initials: M
authors.lastname: Sodemann
authors.forename: Lars
authors.initials: L
authors.lastname: Østergaard
authors.forename: Richard
authors.initials: R
authors.lastname: Adegbola
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sirugo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001118:Argentina / Q000453:epidemiology; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005714:Gambia / Q000453:epidemiology; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation / Q000502:physiology; D005828:Genetics, Population; D006169:Guinea-Bissau / Q000453:epidemiology; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D014397:Tuberculosis, Pulmonary / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D055815:Young Adult; D001741:Black or African American
chemical_list: C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40