A polymorphism in human MR1 is associated with mRNA expression and susceptibility to tuberculosis.

Seshadri, C; Thuong, N T T; Mai, N T H; Bang, N D; Chau, T T H; Lewinsohn, D M; Thwaites, G E; Dunstan, S J; Hawn, T R

Seshadri, C; Thuong, N T T; Mai, N T H; Bang, N D; Chau, T T H; Lewinsohn, D M; Thwaites, G E; Dunstan, S J; Hawn, T R.

Afiliación

Seshadri C; Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA.
Thuong NT; Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Mai NT; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
Bang ND; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Chau TT; Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease, Ho Chi Minh City, Vietnam.
Lewinsohn DM; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Thwaites GE; Division of Pulmonary and Critical Care Medicine, Oregon Health Sciences University, Portland, OR, USA.
Dunstan SJ; Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Hawn TR; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.

Genes Immun ; 18(1): 8-14, 2017 01.

Article en En | MEDLINE | ID: mdl-27881839

RESUMEN

The MR1 antigen-presenting system is conserved among mammals and enables T cells to recognize small molecules produced by bacterial pathogens, including Mycobacterium tuberculosis (M.tb). However, it is not known whether MR1-mediated antigen presentation is important for protective immunity against mycobacterial disease. We hypothesized that genetic control of MR1 expression correlates with clinical outcomes of tuberculosis infection. We performed an MR1 candidate gene association study and identified an intronic single-nucleotide polymorphism (rs1052632) that was significantly associated with susceptibility to tuberculosis in a discovery and validation cohort of Vietnamese adults with tuberculosis. Stratification by site of disease revealed that rs1052632 genotype GG was strongly associated with the development of meningeal tuberculosis (odds ratio=2.99; 95% confidence interval (CI) 1.64-5.43; P=0.00006). Among patients with meningeal disease, absence of the G allele was associated with an increased risk of death (hazard ratio=3.86; 95% CI 1.49-9.98; P=0.005). Variant annotation tools using public databases indicate that rs1052632 is strongly associated with MR1 gene expression in lymphoblastoid cells (P=0.004) and is located within a transcriptional enhancer in epithelial keratinocytes. These data support a role for MR1 in the pathogenesis of human tuberculosis by revealing that rs1052632 is associated with MR1 gene expression and susceptibility to tuberculosis in Vietnam.

Asunto(s)

Predisposición Genética a la Enfermedad; Antígenos de Histocompatibilidad Clase I/genética; Antígenos de Histocompatibilidad Menor/genética; Mycobacterium tuberculosis/aislamiento & purificación; Polimorfismo de Nucleótido Simple/genética; ARN Mensajero/genética; Tuberculosis Pulmonar/genética; Tuberculosis Pulmonar/microbiología; Adulto; Biomarcadores/metabolismo; Estudios de Casos y Controles; Femenino; Estudios de Seguimiento; Genotipo; Humanos; Masculino; Mycobacterium tuberculosis/genética; Pronóstico; Tuberculosis Pulmonar/metabolismo; Vietnam

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis Pulmonar / ARN Mensajero / Antígenos de Histocompatibilidad Clase I / Antígenos de Histocompatibilidad Menor / Predisposición Genética a la Enfermedad / Polimorfismo de Nucleótido Simple / Mycobacterium tuberculosis Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male País/Región como asunto: Asia Idioma: En Revista: Genes Immun Asunto de la revista: ALERGIA E IMUNOLOGIA / BIOLOGIA MOLECULAR Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

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