Our notion was further reinforced by our own discovery in 2018 that the allele frequency of the heterozygous RNF213 p.Arg4810Lys variant was significantly higher in 76 Japanese patients with PAH, compared to that in 79 Japanese supercentenarians who had lived to over 110 years old and never experienced significant health problems [8]. This evidence concerns the gene RNF213 and pulmonary arterial hypertension.