title: Influence of the polymorphism of the DUSP14 gene on the expression of immune-related genes and development of pulmonary tuberculosis.
abstract: Recently, a genome-wide screening identified a functional single-nucleotide polymorphism in dual-specificity phosphatase 14 gene (DUSP14), which was associated with pulmonary tuberculosis (TB) in a West African study. DUSP14 regulates T-cell proliferation and cytokine production in a negative way via dephosphorylation and inactivation of key signaling molecules. The aim of this study is to further explore the possible significance of the DUSP14 polymorphism. Total RNA was extracted from the whole blood of 109 healthcare workers (HCWs) in Vietnam and subjected to quantitative reverse-transcription PCR for DUSP14 and 20 immune-related genes. DUSP14 rs1051838 was genotyped in 502 new pulmonary TB patients and 506 healthy controls. Among disease-free individuals (HCWs), T-helper type-1 (Th1)-related genes, interferon-gamma receptor 2 (IFNGR2) and signal transducer and activator of transcription-1 (STAT1) mRNA levels significantly increased as the number of A alleles of rs1051838 increased, whereas the DUSP14 mRNA level tended to decrease. The AA genotype was associated with protection against active TB in younger patients (⩽45 years old, OR=0.63, 95% CI 0.44-0.90). Our results suggest that a low-expression genotype of DUSP14 accompanied by high transcript levels of Th1 immune-related genes may confer protection against early TB development.
authors.affiliation: Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hijikata
authors.affiliation: Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Matsushita
authors.affiliation: NCGM-BMH Medical Collaboration Center, Hanoi, Vietnam.
authors.forename: N T
authors.initials: NT
authors.lastname: Le Hang
authors.affiliation: Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: P H
authors.initials: PH
authors.lastname: Thuong
authors.affiliation: Department of Biochemistry, Hematology and Blood Transfusion, Hanoi Lung Hospital, Hanoi, Vietnam.
authors.forename: D B
authors.initials: DB
authors.lastname: Tam
authors.affiliation: Hokkaido Pharmaceutical University School of Pharmacy, Hokkaido, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Maeda
authors.affiliation: National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sakurada
authors.affiliation: Hanoi Department of Health, Hanoi, Vietnam.
authors.forename: V C
authors.initials: VC
authors.lastname: Cuong
authors.affiliation: Hanoi Department of Health, Hanoi, Vietnam.
authors.forename: L T
authors.initials: LT
authors.lastname: Lien
authors.affiliation: Department of Pathophysiology and Host Defense, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan.|National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: N
authors.identifier: 0000-0001-8232-9448
authors.initials: N
authors.lastname: Keicho
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D054637:Dual-Specificity Phosphatases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology
chemical_list: C086185:IFNGR2 protein, human; D012333:RNA, Messenger; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D054639:Mitogen-Activated Protein Kinase Phosphatases; C498843:DUSP14 protein, human; D054637:Dual-Specificity Phosphatases