title: Polymorphism in IL1B: IL1B-511 association with tuberculosis and decreased lipopolysaccharide-induced IL-1beta in IFN-gamma primed ex-vivo whole blood assay.
abstract: To determine whether variation in two interleukin 1 family genes (IL1B and interleukin 1 receptor antagonist, IL1RN) is associated with pulmonary tuberculosis (TB), two published polymorphisms at nucleotide positions -511 and +3953 in IL1B and one in the IL1RN 86 bp VNTR were genotyped in 335 smear positive Gambian TB patients, and 298 ethnically matched controls. All individuals were HIV negative. Decreased risk of pulmonary TB was associated with both heterozygosity and homozygosity for the IL1B-511-C allele (OR 0.66, P = 0.027, and OR 0.58, P = 0.015, respectively). Nonetheless, the C allele was present at a frequency of 0.66 in TB cases suggesting that whilst IL-1beta contributes to disease susceptibility, it is not the major factor. There was no association between the IL1B+3953-T/C polymorphism or the 86 bp IL1RN pentallelic repeat and TB in this population. Using an ex-vivo whole blood assay, healthy Gambian individuals who are homozygous for the IL1B-511-T allele failed to exhibit a significant increase in IL-1beta production in response to LPS after IFN-gamma priming.
authors.affiliation: Medical Research Council Laboratories, Fajara, Banjul, The Gambia. aawomoyi@son.umaryland.edu
authors.forename: Agnes A
authors.initials: AA
authors.lastname: Awomoyi
authors.forename: Manhattan
authors.initials: M
authors.lastname: Charurat
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchant
authors.forename: E Nancy
authors.initials: EN
authors.lastname: Miller
authors.forename: Jenefer M
authors.initials: JM
authors.lastname: Blackwell
authors.forename: Keith P W J
authors.initials: KP
authors.lastname: McAdam
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Newport
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005714:Gambia; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D007375:Interleukin-1 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000382:microbiology
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D007371:Interferon-gamma