Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension

Takahiro Hiraide, Masaharu Kataoka, Hisato Suzuki, Yuki Aimi, Tomohiro Chiba, Sarasa Isobe, Yoshinori Katsumata, Shinichi Goto, Kohsuke Kanekura, Yoshitake Yamada, Hidenori Moriyama, Hiroki Kitakata, Jin Endo, Shinsuke Yuasa, Yasumichi Arai, Nobuyoshi Hirose, Toru Satoh, Yoji Hakamata, Motoaki Sano, Shinobu GamouKenjiro Kosaki, Keiichi Fukuda

研究成果: Article査読

21 被引用数 (Scopus)


BACKGROUND: A variant of c.14429G>A (p.Arg4810Lys, rs112735431) in the ring finger protein 213 gene (RNF213; NM_001256071.2) has been recently identified as a risk allele for pulmonary arterial hypertension (PAH). PAH can be added as a new member of RNF213-associated vascular diseases, which include Moyamoya disease and peripheral pulmonary stenosis. Our aim was to identify the clinical features and outcomes of PAH patients with this variant. METHODS: Whole-exome sequencing was performed in 139 idiopathic (or possibly heritable) PAH patients. RESULTS: The RNF213 p.Arg4810Lys variant was identified in a heterozygous state in 11 patients (7.9%). Time-course changes in hemodynamics after combination therapy in the patients with the RNF213 p.Arg4810Lys variant were significantly poorer compared with those carrying the bone morphogenic protein receptor type 2 (BMPR2) mutation (n = 36) (comparison of changes in mean pulmonary arterial pressure, p = 0.007). The event-free rate of death or lung transplantation was significantly poorer in RNF213 p.Arg4810Lys variant carriers than in BMPR2 mutation carriers (5-year event-free rate since the introduction of prostaglandin I2 infusion, 0% vs 93%, respectively; p < 0.001). CONCLUSIONS: Idiopathic PAH patients with the RNF213 p.Arg4810Lys variant are associated with poor clinical outcomes even in recent times. Earlier consideration of lung transplantation might be required for RNF213 p.Arg4810Lys variant carriers who are developing PAH. Documentation of the RNF213 p.Arg4810Lys variant, as well as already known pathogenic genes, such as BMPR2, can provide clinically relevant information for therapeutic strategies, leading to a personalized approach for the treatment of PAH.

ジャーナルJournal of Heart and Lung Transplantation
出版ステータスPublished - 2020 2月

ASJC Scopus subject areas

  • 外科
  • 呼吸器内科
  • 循環器および心血管医学
  • 移植


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