Wang Mei-Tzu, Weng Ken-Pen, Chang Sheng-Kai, Huang Wei-Chun, Chen Lee-Wei
Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
Department of Critical Care Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
Int J Mol Sci. 2024 Feb 27;25(5):2734. doi: 10.3390/ijms25052734.
Asians have a higher carrier rate of pulmonary arterial hypertension (PAH)-related genetic variants than Caucasians do. This study aimed to identify PAH-related genetic variants using whole exome sequencing (WES) in Asian idiopathic and heritable PAH cohorts. A WES library was constructed, and candidate variants were further validated by polymerase chain reaction and Sanger sequencing in the PAH cohort. In a total of 69 patients, the highest incidence of variants was found in the BMPR2, , and genes. Regarding the gene variants, there were two nonsense variants (c.994C>T, p. Arg332*; c.1750C>T, p. Arg584*), one missense variant (c.1478C>T, p. Thr493Ile), and one novel in-frame deletion variant (c.877_888del, p. Leu293_Ser296del). Regarding the variants, there was one likely pathogenic nonsense variant (c.259C>T, p. Gln87*) and two missense variants (c.1207G>A, p. Val403Ile; c.38T>C, p. Leu13Pro). The and variant subgroups had worse hemodynamics. Moreover, the variant patients were younger and had a significantly lower GDF2 value (135.6 ± 36.2 pg/mL, = 0.002) in comparison to the value in the non-/non- mutant group (267.8 ± 185.8 pg/mL). The variant carriers had worse hemodynamics compared to the patients with the non-/non- mutant group. Moreover, there was a significantly lower GDF2 value in the variant carriers compared to the control group. may be a protective or corrected modifier in certain genetic backgrounds.
亚洲人肺动脉高压（PAH）相关基因变异的携带率高于白种人。本研究旨在通过全外显子组测序（WES）在亚洲特发性和遗传性PAH队列中鉴定PAH相关基因变异。构建了WES文库，并在PAH队列中通过聚合酶链反应和桑格测序对候选变异进行进一步验证。在总共69例患者中，发现BMPR2等基因变异的发生率最高。关于该基因变异，有两个无义变异（c.994C>T，p.Arg332*；c.1750C>T，p.Arg584*）、一个错义变异（c.1478C>T，p.Thr493Ile）和一个新的框内缺失变异（c.877_888del，p.Leu293_Ser296del）。关于该变异，有一个可能致病的无义变异（c.259C>T，p.Gln87*）和两个错义变异（c.1207G>A，p.Val403Ile；c.38T>C，p.Leu13Pro）。该和变异亚组的血流动力学较差。此外，与非/非突变组相比，该变异患者更年轻，GDF2值显著更低（135.6±36.2 pg/mL，P = 0.002），非/非突变组的值为（267.8±185.8 pg/mL）。与非/非突变组患者相比，该变异携带者的血流动力学更差。此外，与对照组相比，该变异携带者的GDF2值显著更低。在某些遗传背景下可能是一种保护性或校正性修饰因子。
