Channelopathy Genes in Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a rare, progressive vasculopathy with significant cardiopulmonary morbidity and mortality. The underlying pathogenetic mechanisms are heterogeneous and current therapies aim to decrease pulmonary vascular resistance but no curative treatments are available. C...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/12/2/265 |
| _version_ | 1827656510795153408 |
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| author | Carrie L. Welch Wendy K. Chung |
| author_facet | Carrie L. Welch Wendy K. Chung |
| author_sort | Carrie L. Welch |
| collection | DOAJ |
| description | Pulmonary arterial hypertension (PAH) is a rare, progressive vasculopathy with significant cardiopulmonary morbidity and mortality. The underlying pathogenetic mechanisms are heterogeneous and current therapies aim to decrease pulmonary vascular resistance but no curative treatments are available. Causal genetic variants can be identified in ~13% of adults and 43% of children with PAH. Knowledge of genetic diagnoses can inform clinical management of PAH, including multimodal medical treatment, surgical intervention and transplantation decisions, and screening for associated conditions, as well as risk stratification for family members. Roles for rare variants in three channelopathy genes—<i>ABCC8</i>, <i>ATP13A3</i>, and <i>KCNK3</i>—have been validated in multiple PAH cohorts, and in aggregate explain ~2.7% of PAH cases. Complete or partial loss of function has been demonstrated for PAH-associated variants in <i>ABCC8</i> and <i>KCNK3</i>. Channels can be excellent targets for drugs, and knowledge of mechanisms for channel mutations may provide an opportunity for the development of PAH biomarkers and novel therapeutics for patients with hereditary PAH but also potentially more broadly for all patients with PAH. |
| first_indexed | 2024-03-09T22:30:23Z |
| format | Article |
| id | doaj.art-ea15d96bc1ad4e7a91438ad83a414514 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T22:30:23Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-ea15d96bc1ad4e7a91438ad83a4145142023-11-23T18:59:09ZengMDPI AGBiomolecules2218-273X2022-02-0112226510.3390/biom12020265Channelopathy Genes in Pulmonary Arterial HypertensionCarrie L. Welch0Wendy K. Chung1Department of Pediatrics, Columbia University Irving Medical Center, New York, NY 10032, USADepartment of Pediatrics, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USAPulmonary arterial hypertension (PAH) is a rare, progressive vasculopathy with significant cardiopulmonary morbidity and mortality. The underlying pathogenetic mechanisms are heterogeneous and current therapies aim to decrease pulmonary vascular resistance but no curative treatments are available. Causal genetic variants can be identified in ~13% of adults and 43% of children with PAH. Knowledge of genetic diagnoses can inform clinical management of PAH, including multimodal medical treatment, surgical intervention and transplantation decisions, and screening for associated conditions, as well as risk stratification for family members. Roles for rare variants in three channelopathy genes—<i>ABCC8</i>, <i>ATP13A3</i>, and <i>KCNK3</i>—have been validated in multiple PAH cohorts, and in aggregate explain ~2.7% of PAH cases. Complete or partial loss of function has been demonstrated for PAH-associated variants in <i>ABCC8</i> and <i>KCNK3</i>. Channels can be excellent targets for drugs, and knowledge of mechanisms for channel mutations may provide an opportunity for the development of PAH biomarkers and novel therapeutics for patients with hereditary PAH but also potentially more broadly for all patients with PAH.https://www.mdpi.com/2218-273X/12/2/265channelopathygeneticslung diseasepulmonary arterial hypertension |
| spellingShingle | Carrie L. Welch Wendy K. Chung Channelopathy Genes in Pulmonary Arterial Hypertension Biomolecules channelopathy genetics lung disease pulmonary arterial hypertension |
| title | Channelopathy Genes in Pulmonary Arterial Hypertension |
| title_full | Channelopathy Genes in Pulmonary Arterial Hypertension |
| title_fullStr | Channelopathy Genes in Pulmonary Arterial Hypertension |
| title_full_unstemmed | Channelopathy Genes in Pulmonary Arterial Hypertension |
| title_short | Channelopathy Genes in Pulmonary Arterial Hypertension |
| title_sort | channelopathy genes in pulmonary arterial hypertension |
| topic | channelopathy genetics lung disease pulmonary arterial hypertension |
| url | https://www.mdpi.com/2218-273X/12/2/265 |
| work_keys_str_mv | AT carrielwelch channelopathygenesinpulmonaryarterialhypertension AT wendykchung channelopathygenesinpulmonaryarterialhypertension |