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J Infect Dis. 2015 Jan 15;211(2):317-21. doi: 10.1093/infdis/jiu446. Epub 2014 Aug 20.

Tuberculin skin test negativity is under tight genetic control of chromosomal region 11p14-15 in settings with different tuberculosis endemicities.

Author information

1
McGill International TB Centre Department of Human Genetics Department of Medicine, McGill University, Montreal, Canada.
2
Centre de Lutte Anti-Tuberculeuse, Centre Hospitalier Intercommunal de Créteil, Créteil.
3
Molecular Biology and Human Genetics, MRC Centre for Molecular and Cellular Biology, DST/NRF Centre of Excellence for Biomedical TB Research, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
4
National Center for Genotyping, Genomic Institute, CEA, Evry.
5
Association Clinique et Thérapeutique Infantile du Val de Marne, Saint Maur des Fossés.
6
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163.
7
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute.
8
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch.
9
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch Howard Hughes Medical Institute, Rockefeller University, New York, New York.
10
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U.1163 University Paris Descartes, Sorbonne Paris Cité, Imagine Institute URC, CIC, Necker, and Cochin Hospitals, Paris, France St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch.
11
Pediatric Pneumology Unit, Necker-Enfants-Malades Hospital, AP-HP.

Abstract

A substantial proportion of subjects exposed to a contagious tuberculosis case display lack of tuberculin skin test (TST) reactivity. We previously mapped a major locus (TST1) controlling lack of TST reactivity in families from an area in South Africa where tuberculosis is hyperendemic. Here, we conducted a household tuberculosis contact study in a French area where the endemicity of tuberculosis is low. A genome-wide analysis of TST negativity identified a significant linkage signal (P < 3 × 10(-5)) in close vicinity of TST1. Combined analysis of the 2 samples increased evidence of linkage (P = 2.4 × 10(-6)), further implicating genetic factors located on 11p14-15. This region overlaps the TNF1 locus controlling mycobacteria-driven tumor necrosis factor α production.

KEYWORDS:

genome-wide linkage; human genetics; tuberculin skin test; tuberculosis infection

PMID:
25143445
PMCID:
PMC4279780
DOI:
10.1093/infdis/jiu446
[Indexed for MEDLINE]
Free PMC Article

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