Major Loci on Chromosomes 8q and 3q Control Interferon γ Production Triggered by Bacillus Calmette-Guerin and 6-kDa Early Secretory Antigen Target, Respectively, in Various Populations.
J Infect Dis
; 213(7): 1173-9, 2016 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-26690346
ABSTRACT
BACKGROUND:
Interferon γ (IFN-γ) release assays (IGRAs) provide an in vitro measurement of antimycobacterial immunity that is widely used as a test for Mycobacterium tuberculosis infection. IGRA outcomes are highly heritable in various populations, but the nature of the involved genetic factors remains unknown.METHODS:
We conducted a genome-wide linkage analysis of IGRA phenotypes in families from a tuberculosis household contact study in France and a replication study in families from South Africa to confirm the loci identified.RESULTS:
We identified a major locus on chromosome 8q controlling IFN-γ production in response to stimulation with live bacillus Calmette-Guerin (BCG; LOD score, 3.81; P = 1.40 × 10(-5)). We also detected a second locus, on chromosome 3q, that controlled IFN-γ levels in response to stimulation with 6-kDa early secretory antigen target, when accounting for the IFN-γ production shared with that induced by BCG (LOD score, 3.72; P = 1.8 × 10(-5)). Both loci were replicated in South African families, where tuberculosis is hyperendemic. These loci differ from those previously identified as controlling the response to the tuberculin skin test (TST1 and TST2) and the production of TNF-α (TNF1).CONCLUSIONS:
The identification of 2 new linkage signals in populations of various ethnic origins living in different M. tuberculosis exposure settings provides new clues about the genetic control of human antimycobacterial immunity.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
/
2_ODS3
/
3_ND
Problema de salud:
1_doencas_transmissiveis
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2_enfermedades_transmissibles
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3_neglected_diseases
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3_tuberculosis
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3_zoonosis
Asunto principal:
Proteínas Bacterianas
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Cromosomas Humanos Par 3
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Cromosomas Humanos Par 8
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Regulación Bacteriana de la Expresión Génica
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Interferón gamma
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Mycobacterium bovis
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Antígenos Bacterianos
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Límite:
Female
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Humans
/
Male
País/Región como asunto:
Africa
/
Europa
Idioma:
En
Revista:
J Infect Dis
Año:
2016
Tipo del documento:
Article