Tnfrsf13b c.226g>a (p.gly76ser) as a novel causative mutation for pulmonary arterial hypertension

Yoshiki Shinya, Takahiro Hiraide, Mizuki Momoi, Shinichi Goto, Hisato Suzuki, Yoshinori Katsumata, Yutaka Kurebayashi, Jin Endo, Motoaki Sano, Keiichi Fukuda, Kenjiro Kosaki, Masaharu Kataoka

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Recently, some studies reported the pulmonary artery hypertension (PAH)–associated genes. However, a majority of patients with familial or sporadic PAH lack variants in the known pathogenic genes. In this study, we investigated the new causative gene variants associated with PAH. METHODS AND RESULTS: Whole-exome sequencing in 242 Japanese patients with familial or sporadic PAH identified a heterozygous substitution change involving c.226G>A (p.Gly76Ser) in tumor necrotic factor receptor superfamily 13B gene (TNFRSF13B) in 6 (2.5%) patients. TNFRSF13B controls the differentiation of B cell and secretion of inflammatory cytokines and may be involved in vascular inflammation. In silico structural analysis simulation demonstrated the structural instability of the N-terminal region of the protein synthesized from TNFRSF13B p.Gly76Ser variant. These suggest that the TNFRSF13B p.Gly76Ser variant may be involved in the development of PAH via aberrant inflammation in pulmonary vessels. CONCLUSIONS: TNFRSF13B p.Gly76Ser variant is a candidate of novel causative gene variant for PAH.

Original languageEnglish
Article numbere019245
Pages (from-to)1-4
Number of pages4
JournalJournal of the American Heart Association
Volume10
Issue number5
DOIs
Publication statusPublished - 2021

Keywords

  • Genetics
  • Pulmonary arterial hypertension
  • Structural analysis
  • TNFRSF13B
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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