Tuberculin Skin Test Negativity Is Under Tight Genetic Control of Chromosomal Region 11p14-15 in Settings With Different Tuberculosis Endemicities

• Published in: The Journal of infectious diseases Vol. 211; no. 2; pp. 317 - 321
• Main Authors: Cobat, Aurélie, Poirier, Christine, Hoal, Eileen, Boland-Auge, Anne, de La Rocque, France, Corrard, François, Grange, Ghislain, Migaud, Mélanie, Bustamante, Jacinta, Boisson-Dupuis, Stéphanie, Casanova, Jean-Laurent, Schurr, Erwin, Alcaïs, Alexandre, Delacourt, Christophe, Abel, Laurent
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.01.2015
• Subjects: Adolescent; Adult; BACTERIA; Child; Child, Preschool; Female; Genetic Association Studies; Human health and pathology; Humans; Hypersensitivity, Delayed - genetics; Infant; Infectious diseases; Life Sciences; Linkage Disequilibrium; Major and Brief Reports; Male; Middle Aged; Mycobacterium; Prospective Studies; South Africa; Tuberculin - immunology; Tuberculin Test; Tuberculosis - diagnosis; Young Adult; South Africa; human genetics; tuberculosis infection; tuberculin skin test; genome-wide linkage
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiu446

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 genomewide 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 11pl4-15. This region overlaps the TNF1 locus controlling mycobacteria-driven tumor necrosis factor α production.