The genetic epidemiology and genotype-phenotype correlations among Chinese children with idiopathic and heritable pulmonary arterial hypertension
Abstract Objective This study aims to analyze the genetic characteristics, genotype-phenotype correlation and long-term prognosis of children with idiopathic/hereditary pulmonary arterial hypertension (IPAH/HPAH) in a Chinese tertiary medical center. Methods A retrospective review was conducted for...
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BMC
2025-07-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-025-03249-y |
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| author | Yuan He Qiangqiang Li Chen Zhang Bradley B. Keller Yiping Shen Hong Gu |
| author_facet | Yuan He Qiangqiang Li Chen Zhang Bradley B. Keller Yiping Shen Hong Gu |
| author_sort | Yuan He |
| collection | DOAJ |
| description | Abstract Objective This study aims to analyze the genetic characteristics, genotype-phenotype correlation and long-term prognosis of children with idiopathic/hereditary pulmonary arterial hypertension (IPAH/HPAH) in a Chinese tertiary medical center. Methods A retrospective review was conducted for all children with IPAH/HPAH treated at Beijing Anzhen Hospital over the past 15 years. All patients underwent genetic testing. Results In total, 170 children with IPAH/HPAH were included in the study (females n = 95, 56%), with a median age of diagnosis 6.46 (3.80, 10.70) years. The study population presented with severe conditions at baseline, with 77 patients assessed as clinically high-risk. Genetic testing identified pathogenic variants in 110 patients (64%), with BMPR2, ACVRL1, and TBX4 accounted for the main causal genes. Compared to non-carriers, carriers of pathogenic variants had a higher clinical risk at baseline (54% vs. 30%, p = 0.04). After targeted therapy, carriers experienced greater clinical deterioration (p = 0.008). The overall follow-up duration was 2.68 (1.60, 4.98) years, with the survival rate at 1-, 3-, and 5-year was 93.4%, 86.7%, and 68.6%, respectively. The prognosis of carriers was significantly worse than that of non-carriers (Log-rank p < 0.001). Multivariate Cox regression analysis indicated that pathogenic variants and higher pulmonary vascular resistance index (PVRI) and were associated with a higher risk of death. Conclusion We uncovered a higher rate of pathogenic variants in Chinese pediatric PAH, while targeted therapy improves the overall prognosis of children with PAH, patients with pathogenic variants presented with poorer response to therapy and poorer prognosis. |
| format | Article |
| id | doaj-art-e37f648660f7448385d97e1f1f443fb2 |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Respiratory Research |
| spelling | doaj-art-e37f648660f7448385d97e1f1f443fb22025-08-20T04:01:40ZengBMCRespiratory Research1465-993X2025-07-0126111110.1186/s12931-025-03249-yThe genetic epidemiology and genotype-phenotype correlations among Chinese children with idiopathic and heritable pulmonary arterial hypertensionYuan He0Qiangqiang Li1Chen Zhang2Bradley B. Keller3Yiping Shen4Hong Gu5Department of Pediatric Cardiology, Beijing Anzhen Hospital, Capital Medical UniversityDepartment of Pediatric Cardiology, Beijing Anzhen Hospital, Capital Medical UniversityDepartment of Pediatric Cardiology, Beijing Anzhen Hospital, Capital Medical UniversityCincinnati Children’s Heart Institute, Cincinnati Children’s Hospital Medical CenterDivision of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical SchoolDepartment of Pediatric Cardiology, Beijing Anzhen Hospital, Capital Medical UniversityAbstract Objective This study aims to analyze the genetic characteristics, genotype-phenotype correlation and long-term prognosis of children with idiopathic/hereditary pulmonary arterial hypertension (IPAH/HPAH) in a Chinese tertiary medical center. Methods A retrospective review was conducted for all children with IPAH/HPAH treated at Beijing Anzhen Hospital over the past 15 years. All patients underwent genetic testing. Results In total, 170 children with IPAH/HPAH were included in the study (females n = 95, 56%), with a median age of diagnosis 6.46 (3.80, 10.70) years. The study population presented with severe conditions at baseline, with 77 patients assessed as clinically high-risk. Genetic testing identified pathogenic variants in 110 patients (64%), with BMPR2, ACVRL1, and TBX4 accounted for the main causal genes. Compared to non-carriers, carriers of pathogenic variants had a higher clinical risk at baseline (54% vs. 30%, p = 0.04). After targeted therapy, carriers experienced greater clinical deterioration (p = 0.008). The overall follow-up duration was 2.68 (1.60, 4.98) years, with the survival rate at 1-, 3-, and 5-year was 93.4%, 86.7%, and 68.6%, respectively. The prognosis of carriers was significantly worse than that of non-carriers (Log-rank p < 0.001). Multivariate Cox regression analysis indicated that pathogenic variants and higher pulmonary vascular resistance index (PVRI) and were associated with a higher risk of death. Conclusion We uncovered a higher rate of pathogenic variants in Chinese pediatric PAH, while targeted therapy improves the overall prognosis of children with PAH, patients with pathogenic variants presented with poorer response to therapy and poorer prognosis.https://doi.org/10.1186/s12931-025-03249-yChildrenGenotypePhenotypePrognosisPulmonary arterial hypertensionTreatment |
| spellingShingle | Yuan He Qiangqiang Li Chen Zhang Bradley B. Keller Yiping Shen Hong Gu The genetic epidemiology and genotype-phenotype correlations among Chinese children with idiopathic and heritable pulmonary arterial hypertension Respiratory Research Children Genotype Phenotype Prognosis Pulmonary arterial hypertension Treatment |
| title | The genetic epidemiology and genotype-phenotype correlations among Chinese children with idiopathic and heritable pulmonary arterial hypertension |
| title_full | The genetic epidemiology and genotype-phenotype correlations among Chinese children with idiopathic and heritable pulmonary arterial hypertension |
| title_fullStr | The genetic epidemiology and genotype-phenotype correlations among Chinese children with idiopathic and heritable pulmonary arterial hypertension |
| title_full_unstemmed | The genetic epidemiology and genotype-phenotype correlations among Chinese children with idiopathic and heritable pulmonary arterial hypertension |
| title_short | The genetic epidemiology and genotype-phenotype correlations among Chinese children with idiopathic and heritable pulmonary arterial hypertension |
| title_sort | genetic epidemiology and genotype phenotype correlations among chinese children with idiopathic and heritable pulmonary arterial hypertension |
| topic | Children Genotype Phenotype Prognosis Pulmonary arterial hypertension Treatment |
| url | https://doi.org/10.1186/s12931-025-03249-y |
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