Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Jul 15;178(2):203-7.
doi: 10.1164/rccm.200710-1554OC. Epub 2008 Apr 17.

Mapping of a novel susceptibility locus suggests a role for MC3R and CTSZ in human tuberculosis

Graham S Cooke  1 , Sarah J Campbell, Steve Bennett, Christian Lienhardt, Keith P W J McAdam, Giorgio Sirugo, Oumou Sow, Per Gustafson, Frank Mwangulu, Paul van Helden, Paul Fine, Eileen G Hoal, Adrian V S Hill
Affiliations

Mapping of a novel susceptibility locus suggests a role for MC3R and CTSZ in human tuberculosis

Graham S Cooke et al. Am J Respir Crit Care Med. .

Erratum in

  • Am J Respir Crit Care Med. 2009 Apr 1;179(7):624

Abstract

Rationale: Tuberculosis remains a major cause of morbidity and mortality in the developing world. A better understanding of the mechanisms of disease protection could allow novel strategies to disease management and control.

Objectives: To identify human genomic loci with evidence of linkage to tuberculosis susceptibility and, within these loci, to identify individual genes influencing tuberculosis susceptibility.

Methods: Affected sibling pair analysis in South African and Malawian populations. Independent case-control study in West Africa.

Measurements and main results: Two novel putative loci for tuberculosis susceptibility are identified: chromosome 6p21-q23 and chromosome 20q13.31-33--the latter with the strongest evidence for any locus reported to date in human tuberculosis (single point LOD score of 3.1, P = 10(-4), with a maximum likelihood score [MLS] of 2.8). An independent, multistage genetic association study in West African populations mapped this latter region in detail, finding evidence that variation in the melanocortin 3 receptor (MC3R) and cathepsin Z (CTSZ) genes play a role in the pathogenesis of tuberculosis.

Conclusions: These results demonstrate how a genomewide approach to the complex phenotype of human tuberculosis can identify novel targets for further research.

PubMed Disclaimer

Figures

<b>Figure 1.</b>
Figure 1.
Multipoint mapping of chromosome 20 for all populations studied. Peak of linkage corresponds to marker 20s171.
See this image and copyright information in PMC

References

    1. Brahmajothi V, Pitchappan RM, Kakkanaiah VN, Sashidhar M, Rajaram K, Ramu S, Palanimurugan K, Paramasivan CN, Prabhakar R. Association of pulmonary tuberculosis and HLA in south India. Tubercle 1991;72:123–132. - PubMed
    1. Singh SP, Mehra NK, Dingley HB, Pande JN, Vaidya MC. Human leukocyte antigen (HLA)-linked control of susceptibility to pulmonary tuberculosis and association with HLA-DR types. J Infect Dis 1983;148:676–681. - PubMed
    1. Ravikumar M, Dheenadhayalan V, Rajaram K, Lakshmi SS, Kumaran PP, Paramasivan CN, Balakrishnan K, Pitchappan RM. Associations of HLA-DRB1, DQB1 and DPB1 alleles with pulmonary tuberculosis in south India. Tuber Lung Dis 1999;79:309–317. - PubMed
    1. Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV. Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans. N Engl J Med 1998;338:640–644. - PubMed
    1. Awomoyi AA, Marchant A, Howson JM, McAdam KP, Blackwell JM, Newport MJ. Interleukin-10, polymorphism in SLC11A1 (formerly NRAMP1), and susceptibility to tuberculosis. J Infect Dis 2002;186:1808–1814. - PubMed

Publication types

MeSH terms