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Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease.
Namkoong, Ho; Omae, Yosuke; Asakura, Takanori; Ishii, Makoto; Suzuki, Shoji; Morimoto, Kozo; Kawai, Yosuke; Emoto, Katsura; Oler, Andrew J; Szymanski, Eva P; Yoshida, Mitsunori; Matsuda, Shuichi; Yagi, Kazuma; Hase, Isano; Nishimura, Tomoyasu; Sasaki, Yuka; Asami, Takahiro; Shiomi, Tetsuya; Matsubara, Hiroaki; Shimada, Hisato; Hamamoto, Junko; Jhun, Byung Woo; Kim, Su-Young; Huh, Hee Jae; Won, Hong-Hee; Ato, Manabu; Kosaki, Kenjiro; Betsuyaku, Tomoko; Fukunaga, Koichi; Kurashima, Atsuyuki; Tettelin, Hervé; Yanai, Hideki; Mahasirimongkol, Surakameth; Olivier, Kenneth N; Hoshino, Yoshihiko; Koh, Won-Jung; Holland, Steven M; Tokunaga, Katsushi; Hasegawa, Naoki.
  • Namkoong H; Division of Pulmonary Medicine, Dept of Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Omae Y; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA.
  • Asakura T; JSPS Overseas Research Fellow, Japan Society for the Promotion of Science, Tokyo, Japan.
  • Ishii M; H. Namkoong and Y. Omae are co-first authors.
  • Suzuki S; H. Namkoong, N. Hasegawa and K. Tokunaga contributed equally to this article as lead authors and supervised the work.
  • Morimoto K; Dept of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Kawai Y; Genome Medical Science Project (Toyama), National Center for Global Health and Medicine, Tokyo, Japan.
  • Emoto K; H. Namkoong and Y. Omae are co-first authors.
  • Oler AJ; Division of Pulmonary Medicine, Dept of Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Szymanski EP; Dept of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
  • Yoshida M; Division of Pulmonary Medicine, Dept of Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Matsuda S; Division of Pulmonary Medicine, Dept of Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Yagi K; Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.
  • Hase I; Dept of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Nishimura T; Genome Medical Science Project (Toyama), National Center for Global Health and Medicine, Tokyo, Japan.
  • Sasaki Y; Dept of Pathology, Keio University School of Medicine, Tokyo, Japan.
  • Asami T; Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA.
  • Shiomi T; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA.
  • Matsubara H; Dept of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
  • Shimada H; Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.
  • Hamamoto J; Division of Pulmonary Medicine, Dept of Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Jhun BW; Dept of Respiratory Medicine, National Hospital Organization Utsunomiya Hospital, Tochigi, Japan.
  • Kim SY; Keio University Health Center, Tokyo, Japan.
  • Huh HJ; Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.
  • Won HH; Division of Pulmonary Medicine, Dept of Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Ato M; Dept of Pulmonary Medicine, Keiyu Hospital, Kanagawa, Japan.
  • Kosaki K; Dept of Pulmonary Medicine, Fussa Hospital, Tokyo, Japan.
  • Betsuyaku T; Dept of Pulmonary Medicine, Kawasaki Municipal Ida Hospital, Kanagawa, Japan.
  • Fukunaga K; Division of Pulmonary Medicine, Dept of Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Kurashima A; Division of Pulmonary and Critical Care Medicine, Dept of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
  • Tettelin H; Division of Pulmonary and Critical Care Medicine, Dept of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
  • Yanai H; Dept of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
  • Mahasirimongkol S; Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, South Korea.
  • Olivier KN; Dept of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
  • Hoshino Y; Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
  • Koh WJ; Division of Pulmonary Medicine, Dept of Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Holland SM; Division of Pulmonary Medicine, Dept of Medicine, Keio University School of Medicine, Tokyo, Japan.
  • Tokunaga K; Respiratory Disease Center, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Tokyo, Japan.
  • Hasegawa N; Dept of Microbiology and Immunology, School of Medicine, University of Maryland, Bethesda, MD, USA.
Eur Respir J ; 58(2)2021 08.
Article en En | MEDLINE | ID: mdl-33542050
ABSTRACT
RATIONALE Nontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear.

OBJECTIVES:

We aimed to identify host susceptibility loci for Mycobacterium avium complex (MAC), the most common NTM pathogen.

METHODS:

This genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping.

RESULTS:

The GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64×10-13, OR 0.54), which is in an intronic region of the calcineurin-like EF-hand protein 2 (CHP2). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. Additionally, this SNP was significantly associated with the disease in patients of Korean (p=2.18×10-12, OR 0.54) and European (p=5.12×10-03, OR 0.63) ancestry.

CONCLUSIONS:

We identified rs109592 in the CHP2 locus as a susceptibility marker for pulmonary MAC disease.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Infección por Mycobacterium avium-intracellulare / Enfermedades Pulmonares / Infecciones por Mycobacterium no Tuberculosas Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Año: 2021 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Infección por Mycobacterium avium-intracellulare / Enfermedades Pulmonares / Infecciones por Mycobacterium no Tuberculosas Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Año: 2021 Tipo del documento: Article