PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high‐altitude exposure: A self‐controlled study
Abstract Background Left cardiac pumping function determines the compensatory capacity of the cardiovascular system following acute high‐altitude exposure. Variations in cardiac output (CO) at high altitude are inconsistent between individuals, and genetic susceptibility may play a crucial role. We...
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| Format: | Article |
| Language: | English |
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Wiley
2019-10-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.919 |
| _version_ | 1797301105594466304 |
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| author | Jie Yang Chuan Liu Zhang Jihang Jie Yu Limeng Dai Xiaohan Ding Youzhu Qiu Sanjiu Yu Yuanqi Yang Yuzhang Wu Lan Huang |
| author_facet | Jie Yang Chuan Liu Zhang Jihang Jie Yu Limeng Dai Xiaohan Ding Youzhu Qiu Sanjiu Yu Yuanqi Yang Yuzhang Wu Lan Huang |
| author_sort | Jie Yang |
| collection | DOAJ |
| description | Abstract Background Left cardiac pumping function determines the compensatory capacity of the cardiovascular system following acute high‐altitude exposure. Variations in cardiac output (CO) at high altitude are inconsistent between individuals, and genetic susceptibility may play a crucial role. We sought to identify genetic causes of cardiac pumping function variations and describe the genotype–phenotype correlations. Methods A total of 151 young male volunteers were recruited and transferred to Lhasa (3,700 m) from Chengdu (<500 m) by plane. Genetic information related to hypoxic signaling and cardiovascular‐related pathways was collected before departure. Echocardiography was performed both before departure and 24 hr after arrival at high altitude. Results Here we reported that PPARA variants were closely related to high‐altitude cardiac function. The variants of rs6520015 C‐allele and rs7292407 A‐allele significantly increased the risk for cardiac pumping function reductions following acute high‐altitude exposure. In addition, the individuals carrying haplotypes in PPARA, namely, rs135538 C‐allele, rs4253623 A‐allele, rs6520015 C‐allele and rs7292407 A‐allele (C‐A‐C‐A), suffered a 7.27‐fold risk for cardiac pumping function reduction (95% CI: 2.39–22.15, p = .0006) compared with those carrying the wild‐type haplotype. Conclusions This self‐controlled study revealed that PPARA variations significantly increased the risk for cardiac pumping function reductions following acute high‐altitude exposure, providing a potential predictive marker before high‐altitude exposure and targets in mechanistic studies. |
| first_indexed | 2024-03-07T23:16:37Z |
| format | Article |
| id | doaj.art-19507107914d4d98aada21ca242b4605 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:16:37Z |
| publishDate | 2019-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-19507107914d4d98aada21ca242b46052024-02-21T10:29:27ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-10-01710n/an/a10.1002/mgg3.919PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high‐altitude exposure: A self‐controlled studyJie Yang0Chuan Liu1Zhang Jihang2Jie Yu3Limeng Dai4Xiaohan Ding5Youzhu Qiu6Sanjiu Yu7Yuanqi Yang8Yuzhang Wu9Lan Huang10Department of Cardiology the Second Affiliated Hospital, Army Medical University (Third Military Medical University) Chongqing PR ChinaDepartment of Cardiology the Second Affiliated Hospital, Army Medical University (Third Military Medical University) Chongqing PR ChinaDepartment of Cardiology the Second Affiliated Hospital, Army Medical University (Third Military Medical University) Chongqing PR ChinaDepartment of Cardiology the Second Affiliated Hospital, Army Medical University (Third Military Medical University) Chongqing PR ChinaDepartment of Medical Genetics, College of Basic Medical Science Army Medical University (Third Military Medical University) Chongqing PR ChinaDepartment of Cardiology the Second Affiliated Hospital, Army Medical University (Third Military Medical University) Chongqing PR ChinaDepartment of Cardiology the Second Affiliated Hospital, Army Medical University (Third Military Medical University) Chongqing PR ChinaDepartment of Cardiology the Second Affiliated Hospital, Army Medical University (Third Military Medical University) Chongqing PR ChinaDepartment of Cardiology the Second Affiliated Hospital, Army Medical University (Third Military Medical University) Chongqing PR ChinaInstitute of Immunology Army Medical University (Third Military Medical University) Chongqing PR ChinaDepartment of Cardiology the Second Affiliated Hospital, Army Medical University (Third Military Medical University) Chongqing PR ChinaAbstract Background Left cardiac pumping function determines the compensatory capacity of the cardiovascular system following acute high‐altitude exposure. Variations in cardiac output (CO) at high altitude are inconsistent between individuals, and genetic susceptibility may play a crucial role. We sought to identify genetic causes of cardiac pumping function variations and describe the genotype–phenotype correlations. Methods A total of 151 young male volunteers were recruited and transferred to Lhasa (3,700 m) from Chengdu (<500 m) by plane. Genetic information related to hypoxic signaling and cardiovascular‐related pathways was collected before departure. Echocardiography was performed both before departure and 24 hr after arrival at high altitude. Results Here we reported that PPARA variants were closely related to high‐altitude cardiac function. The variants of rs6520015 C‐allele and rs7292407 A‐allele significantly increased the risk for cardiac pumping function reductions following acute high‐altitude exposure. In addition, the individuals carrying haplotypes in PPARA, namely, rs135538 C‐allele, rs4253623 A‐allele, rs6520015 C‐allele and rs7292407 A‐allele (C‐A‐C‐A), suffered a 7.27‐fold risk for cardiac pumping function reduction (95% CI: 2.39–22.15, p = .0006) compared with those carrying the wild‐type haplotype. Conclusions This self‐controlled study revealed that PPARA variations significantly increased the risk for cardiac pumping function reductions following acute high‐altitude exposure, providing a potential predictive marker before high‐altitude exposure and targets in mechanistic studies.https://doi.org/10.1002/mgg3.919cardiac functiongenotype–phenotype correlationhaplotypeshigh altitudePPARA |
| spellingShingle | Jie Yang Chuan Liu Zhang Jihang Jie Yu Limeng Dai Xiaohan Ding Youzhu Qiu Sanjiu Yu Yuanqi Yang Yuzhang Wu Lan Huang PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high‐altitude exposure: A self‐controlled study Molecular Genetics & Genomic Medicine cardiac function genotype–phenotype correlation haplotypes high altitude PPARA |
| title | PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high‐altitude exposure: A self‐controlled study |
| title_full | PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high‐altitude exposure: A self‐controlled study |
| title_fullStr | PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high‐altitude exposure: A self‐controlled study |
| title_full_unstemmed | PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high‐altitude exposure: A self‐controlled study |
| title_short | PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high‐altitude exposure: A self‐controlled study |
| title_sort | ppara genetic variants increase the risk for cardiac pumping function reductions following acute high altitude exposure a self controlled study |
| topic | cardiac function genotype–phenotype correlation haplotypes high altitude PPARA |
| url | https://doi.org/10.1002/mgg3.919 |
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