Find in Library

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, <i>ATP13A3</i>, and <i>GDF2</i> genes. Regarding the <i>BMPR2</i> 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 <i>GDF2</i> 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 <i>BMPR2</i> and <i>GDF2</i> variant subgroups had worse hemodynamics. Moreover, the <i>GDF2</i> variant patients were younger and had a significantly lower GDF2 value (135.6 ± 36.2 pg/mL, <i>p</i> = 0.002) in comparison to the value in the non-<i>BMPR2</i>/non-<i>GDF2</i> mutant group (267.8 ± 185.8 pg/mL). The <i>BMPR2</i> variant carriers had worse hemodynamics compared to the patients with the non-<i>BMPR2</i>/non-<i>GDF2</i> mutant group. Moreover, there was a significantly lower GDF2 value in the <i>GDF2</i> variant carriers compared to the control group. <i>GDF2</i> may be a protective or corrected modifier in certain genetic backgrounds.