title: Genetic and shared environmental influences on interferon-γ production in response to Mycobacterium tuberculosis antigens in a Ugandan population.
abstract: Interferon-γ (IFN-γ) is a key cytokine in the immune response to Mycobacterium tuberculosis (Mtb). Many studies established IFN-γ responses are influenced by host genetics, however differed widely by the study design and heritability estimation method. We estimated heritability of IFN-γ responses to Mtb culture filtrate (CF), ESAT-6, and Antigen 85B (Ag85B) in 1,104 Ugandans from a household contact study. Our method separately evaluates shared environmental and genetic variance, therefore heritability estimates were not upwardly biased, ranging from 11.6% for Ag85B to 22.9% for CF. Subset analyses of individuals with latent Mtb infection or without human immunodeficiency virus infection yielded higher heritability estimates, suggesting 10-30% of variation in IFN-γ is caused by a shared environment. Immunosuppression does not negate the role of genetics on IFN-γ response. These estimates are remarkably close to those reported for components of the innate immune response. These findings have implications for the interpretation of IFN-γ response assays and vaccine studies.
authors: Department of Medicine, Case Western Reserve University, Cleveland, OH, USA. li.tao@case.edu
authors: Li
authors: L
authors: Tao
authors: Sarah
authors: S
authors: Zalwango
authors: Keith
authors: K
authors: Chervenak
authors: Bonnie
authors: B
authors: Thiel
authors: Lashaunda L
authors: LL
authors: Malone
authors: Feiyou
authors: F
authors: Qiu
authors: Harriet
authors: H
authors: Mayanja-Kizza
authors: W Henry
authors: WH
authors: Boom
authors: Catherine M
authors: CM
authors: Stein
mesh_terms: D000217:Acyltransferases / Q000276:immunology; D000293:Adolescent; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007109:Immunity / Q000235:genetics; D007223:Infant; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014454:Uganda
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis
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