Your browser doesn't support javascript.
loading
Genetic determinants of risk in autoimmune pulmonary alveolar proteinosis.
Sakaue, Saori; Yamaguchi, Etsuro; Inoue, Yoshikazu; Takahashi, Meiko; Hirata, Jun; Suzuki, Ken; Ito, Satoru; Arai, Toru; Hirose, Masaki; Tanino, Yoshinori; Nikaido, Takefumi; Ichiwata, Toshio; Ohkouchi, Shinya; Hirano, Taizou; Takada, Toshinori; Miyawaki, Satoru; Dofuku, Shogo; Maeda, Yuichi; Nii, Takuro; Kishikawa, Toshihiro; Ogawa, Kotaro; Masuda, Tatsuo; Yamamoto, Kenichi; Sonehara, Kyuto; Tazawa, Ryushi; Morimoto, Konosuke; Takaki, Masahiro; Konno, Satoshi; Suzuki, Masaru; Tomii, Keisuke; Nakagawa, Atsushi; Handa, Tomohiro; Tanizawa, Kiminobu; Ishii, Haruyuki; Ishida, Manabu; Kato, Toshiyuki; Takeda, Naoya; Yokomura, Koshi; Matsui, Takashi; Watanabe, Masaki; Inoue, Hiromasa; Imaizumi, Kazuyoshi; Goto, Yasuhiro; Kida, Hiroshi; Fujisawa, Tomoyuki; Suda, Takafumi; Yamada, Takashi; Satake, Yasuomi; Ibata, Hidenori; Hizawa, Nobuyuki.
Afiliación
  • Sakaue S; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Yamaguchi E; Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan.
  • Inoue Y; Center for Data Sciences, Harvard Medical School, Boston, USA.
  • Takahashi M; Divisions of Genetics and Rheumatology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
  • Hirata J; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA.
  • Suzuki K; Division of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Aichi, Japan.
  • Ito S; Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan.
  • Arai T; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Hirose M; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Tanino Y; Pharmaceutical Discovery Research Laboratories, TEIJIN PHARMA LIMITED, Hino, Japan.
  • Nikaido T; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Ichiwata T; Division of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical University, Aichi, Japan.
  • Ohkouchi S; Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan.
  • Hirano T; Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan.
  • Takada T; Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan.
  • Miyawaki S; Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan.
  • Dofuku S; Department Respiratory Medicine, Tokyo Medical University, Tokyo, Japan.
  • Maeda Y; Occupational Health, Graduate School of Medicine, Tohoku University, Miyagi, Japan.
  • Nii T; Respiratory Medicine, School of Medicine, Tohoku University, Miyagi, Japan.
  • Kishikawa T; Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
  • Ogawa K; Department of Neurosurgery, Faculty of Medicine, the University of Tokyo, Tokyo, Japan.
  • Masuda T; Department of Neurosurgery, Faculty of Medicine, the University of Tokyo, Tokyo, Japan.
  • Yamamoto K; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Sonehara K; Laboratory of Immune Regulation, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Tazawa R; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Morimoto K; Laboratory of Immune Regulation, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Takaki M; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Konno S; Department of Otorhinolaryngology - Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
  • Suzuki M; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Tomii K; Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Nakagawa A; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Handa T; Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan.
  • Tanizawa K; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Ishii H; Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Ishida M; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan.
  • Kato T; Student Support and Health Administration Organization, Tokyo Medical and Dental University, Tokyo, Japan.
  • Takeda N; Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
  • Yokomura K; Department of Infectious Diseases, Nagasaki University Hospital, Nagasaki University, Nagasaki, Japan.
  • Matsui T; Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
  • Watanabe M; Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
  • Inoue H; Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
  • Imaizumi K; Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
  • Goto Y; Department of Advanced Medicine for Respiratory Failure, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Kida H; Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Fujisawa T; Department of Respiratory Medicine, Kyorin University, Mitaka, Japan.
  • Suda T; Department of Respiratory Medicine, Kyorin University, Mitaka, Japan.
  • Yamada T; Department of Respiratory Medicine and Allergology, Kariya Toyota General Hospital, Kariya, Japan.
  • Satake Y; Department of Respiratory Medicine and Allergology, Kariya Toyota General Hospital, Kariya, Japan.
  • Ibata H; Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, Hamamatsu, Japan.
  • Hizawa N; Department of Respiratory Medicine, Respiratory Disease Center, Seirei Mikatahara General Hospital, Hamamatsu, Japan.
Nat Commun ; 12(1): 1032, 2021 02 15.
Article en En | MEDLINE | ID: mdl-33589587
Pulmonary alveolar proteinosis (PAP) is a devastating lung disease caused by abnormal surfactant homeostasis, with a prevalence of 6-7 cases per million population worldwide. While mutations causing hereditary PAP have been reported, the genetic basis contributing to autoimmune PAP (aPAP) has not been thoroughly investigated. Here, we conducted a genome-wide association study of aPAP in 198 patients and 395 control participants of Japanese ancestry. The common genetic variant, rs138024423 at 6p21, in the major-histocompatibility-complex (MHC) region was significantly associated with disease risk (Odds ratio [OR] = 5.2; P = 2.4 × 10-12). HLA fine-mapping revealed that the common HLA class II allele, HLA-DRB1*08:03, strongly drove this signal (OR = 4.8; P = 4.8 × 10-12), followed by an additional independent risk allele at HLA-DPß1 amino acid position 8 (OR = 0.28; P = 3.4 × 10-7). HLA-DRB1*08:03 was also associated with an increased level of anti-GM-CSF antibody, a key driver of the disease (ß = 0.32; P = 0.035). Our study demonstrated a heritable component of aPAP, suggesting an underlying genetic predisposition toward an abnormal antibody production.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteinosis Alveolar Pulmonar / Autoanticuerpos / Enfermedades Autoinmunes / Factor Estimulante de Colonias de Granulocitos y Macrófagos / Predisposición Genética a la Enfermedad / Cadenas HLA-DRB1 Tipo de estudio: Etiology_studies / Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteinosis Alveolar Pulmonar / Autoanticuerpos / Enfermedades Autoinmunes / Factor Estimulante de Colonias de Granulocitos y Macrófagos / Predisposición Genética a la Enfermedad / Cadenas HLA-DRB1 Tipo de estudio: Etiology_studies / Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged País/Región como asunto: Asia Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido