Major Loci on Chromosomes 8q and 3q Control Interferon gamma Production Triggered by Bacillus Calmette-Guerin and 6-kDa Early Secretory Antigen Target, Respectively, in Various Populations

作者：Jabot Hanin Fabienne; Cobat Aurelie; Feinberg Jacqueline; Grange Ghislain; Remus Natascha; Poirier Christine; Boland Auge Anne; Besse Celine; Bustamante Jacinta; Boisson Dupuis Stephanie; Casanova Jean Laurent; Schurr Erwin; Alcais Alexandre; Hoal Eileen G; Delacourt Christophe; Abel Laurent^*

来源：Journal of Infectious Diseases, 2016, 213(7): 1173-1179.

DOI：10.1093/infdis/jiv757

• tuberculosis
• genetic linkage analysis
• interferon gamma release assays
• mycobacteria
• genetic control

Background. Interferon gamma (IFN-gamma) 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-gamma production in response to stimulation with live bacillus Calmette-Guerin (BCG; LOD score, 3.81; P = 1.40 x 10(-5)). We also detected a second locus, on chromosome 3q, that controlled IFN-gamma levels in response to stimulation with 6-kDa early secretory antigen target, when accounting for the IFN-gamma production shared with that induced by BCG (LOD score, 3.72; P = 1.8 x 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-alpha (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.

• 出版日期2016-4-1
• 单位中国地震局