Published ahead of print on May 11, 2006, doi:10.1164/rccm.200601-088OC Am. J. Respir. Crit. Care Med., Volume 174, Number 3, August 2006, 339-343 A more recent version of this article appeared on August 1, 2006
Submitted on January 22, 2006 Polymorphism within the Interferon Gamma/Receptor Complex is Associated with Pulmonary TuberculosisGraham S Cooke1*,1 University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom, 2 Medical Research Council Laboratories, Fajara, Gambia, 3 Danish Epidemiology Science Centre, Bissau, Guinea-Bissau, 4 CHU Ignace Deen, Conakry, Republique de Guinee, 5 London School of Hygiene and Tropical Medicine, London, United Kingdom, 6 Medical Research Council Laboratories, Fajara, Gambia; Institut de Recherche pour le Developpement (IRD), UMR 145, Dakar, Senegal * To whom correspondence should be addressed. E-mail: grahamscooke{at}hotmail.com.
Rationale Interferon-gamma is of central interest in the study of tuberculosis. A number of single gene mutations have been identified in the interferon-gamma signalling pathway that predispose to severe mycobacterial disease, but the relevance of polymorphism within these genes to the common phenotype of tuberculosis remains unclear.
Methods 1301 individuals were included in a large, detailed study of West African populations with pulmonary tuberculosis. We investigated disease association with the genes encoding interferon-gamma and its' receptor subunits (IFNG, IFNGR1 and IFNGR2).
Results Within the IFNG gene, two promoter variants showed evidence of novel disease association; -1616GG (OR 1.49 95%C.I. 1.11-2.00, P = 0.008) and +3234TT (OR 1.40 95%C.I. 1.09-1.80 P = 0.009). The +874AA genotype was not significantly more frequent amongst cases over controls (OR 1.16 95%C.I. 0.89-1.51 P = 0.25). In addition, novel disease association was also found with the -56CC genotype of the IFNGR1 promoter (OR 0.75 95%C.I. 0.57-0.99 P = 0.041). No disease association was seen with the IFNGR2 locus.
Conclusions These results provide evidence of a significant role for genetic variation at the IFNG locus and provide detailed understanding of the genetic mechanisms underlying this association. The disease association with IFNGR1 is novel and together these findings support the hypothesis that genetically determined variation in both IFN- Key words: interferon-gamma, tuberculosis, polymorphism, receptor
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
production and responsiveness influence the risk of developing tuberculosis.
