Hemodynamic and Clinical Profiles of Pulmonary Arterial Hypertension Patients with GDF2 and BMPR2 Variants.

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.