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Polymorphism in IL1B: IL1B—511 association with tuberculosis and decreased lipopolysaccharide-induced IL-1ß in IFN- primed ex-vivo whole blood assay

Medical Research Council Laboratories, Fajara, Banjul, The Gambia, Department of Microbiology and Immunology, School of Medicine, University of Maryland Baltimore, Baltimore, Maryland, USA, aawomoyi{at}som.umaryland.edu

Manhattan Charurat

Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, Maryland, USA

Arnaud Marchant

Medical Research Council Laboratories, Fajara, Banjul, The Gambia

E. Nancy Miller

Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, UK

Jenefer M. Blackwell

Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, UK

Keith P.W.J. McAdam

Medical Research Council Laboratories, Fajara, Banjul, The Gambia

Melanie J. Newport

Medical Research Council Laboratories, Fajara, Banjul, The Gambia, Department of Medicine, Brighton and Sussex Medical School, Brighton, UK

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-1ß 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-1ß production in response to LPS after IFN-ypriming.

Key Words: IL1B polymorphism • interleukin-1ß • tuberculosis • ex-vivo whole blood assay

Journal of Endotoxin Research, Vol. 11, No. 5, 281-286 (2005)
DOI: 10.1177/09680519050110050401


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