Genetic determinants of risk in autoimmune pulmonary alveolar proteinosis

Saori Sakaue, Etsuro Yamaguchi, Yoshikazu Inoue, Meiko Takahashi, Jun Hirata, Ken Suzuki, Satoru Ito, Toru Arai, Masaki Hirose, Yoshinori Tanino, Takefumi Nikaido, Toshio Ichiwata, Shinya Ohkouchi, Taizou Hirano, Toshinori Takada, Satoru Miyawaki, Shogo Dofuku, Yuichi Maeda, Takuro Nii, Toshihiro KishikawaKotaro Ogawa, Tatsuo Masuda, Kenichi Yamamoto, Kyuto Sonehara, Ryushi Tazawa, Konosuke Morimoto, Masahiro Takaki, Satoshi Konno, Masaru Suzuki, Keisuke Tomii, Atsushi Nakagawa, Tomohiro Handa, Kiminobu Tanizawa, Haruyuki Ishii, Manabu Ishida, Toshiyuki Kato, Naoya Takeda, Koshi Yokomura, Takashi Matsui, Masaki Watanabe, Hiromasa Inoue, Kazuyoshi Imaizumi, Yasuhiro Goto, Hiroshi Kida, Tomoyuki Fujisawa, Takafumi Suda, Takashi Yamada, Yasuomi Satake, Hidenori Ibata, Nobuyuki Hizawa, Hideki Mochizuki, Atsushi Kumanogoh, Fumihiko Matsuda, Koh Nakata, Tomomitsu Hirota, Mayumi Tamari, Yukinori Okada

研究成果: Article査読

1 被引用数 (Scopus)

抄録

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-DPβ1 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 (β = 0.32; P = 0.035). Our study demonstrated a heritable component of aPAP, suggesting an underlying genetic predisposition toward an abnormal antibody production.

本文言語English
論文番号1032
ジャーナルNature communications
12
1
DOI
出版ステータスPublished - 12-2021

All Science Journal Classification (ASJC) codes

  • 化学 (全般)
  • 生化学、遺伝学、分子生物学(全般)
  • 物理学および天文学(全般)

フィンガープリント

「Genetic determinants of risk in autoimmune pulmonary alveolar proteinosis」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル