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No association between interferon- receptor-1 gene polymorphism and pulmonary tuberculosis in a Gambian population sample

¹ MRC Laboratories, Fajara, The Gambia
² Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK
³ Wellcome Trust Centre for Human Genetics, Oxford, UK
⁴ Department of Medicine, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK

Correspondence to:
Correspondence to:
Dr M Newport
Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke’s Hospital, Cambridge CB2 2XY, UK; Melanie.newport{at}cimr.cam.ac.uk

Background: Tuberculosis (TB) is a major global cause of mortality and morbidity, and host genetic factors influence disease susceptibility. Interferon- mediates immunity to mycobacteria and rare mutations in the interferon- receptor-1 gene (IFNGR1) result in increased susceptibility to mycobacterial infection, including TB, in affected families. The role of genetic variation in IFNGR1 in susceptibility to common mycobacterial diseases such as pulmonary TB in outbred populations has not previously been investigated.

Methods: The association between IFNGR1 and susceptibility to pulmonary TB was investigated in a Gambian adult population sample using a case-control study design. The coding and promoter regions of IFNGR1 were sequenced in 32 patients with pulmonary TB, and the frequencies of six common IFNGR1 polymorphisms were determined using PCR based methods in 320 smear positive TB cases and 320 matched controls. Haplotypes were estimated from the genotype data using the expectation-maximisation algorithm.

Results: There was no association between the IFNGR1 variants studied and TB in this Gambian population sample. Three common haplotypes were identified within the study population, none of which was associated with TB.

Conclusions: These data represent an important negative finding and suggest that, while IFNGR1 is implicated in rare Mendelian susceptibility to mycobacterial disease, the common variants studied here do not have a major influence on susceptibility to pulmonary TB in The Gambian population.

Keywords: genetics; interferon-gamma receptor-1 (IFNGR1); tuberculosis

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