Circulating resistin levels and mutation burden of the RETN gene variants predict long-term mortality in a Taiwanese population
Abstract Human resistin is a proinflammatory cytokine involving the development and progression of cancer and cardiovascular diseases. However, prediction of long-term outcome using circulating resistin level and its genetic determinants in a population-based study remain to be explored. After genom...
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Nature Portfolio
2025-01-01
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| author | Lung-An Hsu Ming-Sheng Teng Semon Wu Mei-Siou Liao Hsin-Hua Chou Yu-Lin Ko |
| author_facet | Lung-An Hsu Ming-Sheng Teng Semon Wu Mei-Siou Liao Hsin-Hua Chou Yu-Lin Ko |
| author_sort | Lung-An Hsu |
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| description | Abstract Human resistin is a proinflammatory cytokine involving the development and progression of cancer and cardiovascular diseases. However, prediction of long-term outcome using circulating resistin level and its genetic determinants in a population-based study remain to be explored. After genome-wide association study (GWAS), DNA methylation (DNAm) analysis and functional assays of a RETN rs370006313 variant, we tested whether resistin level and its genetic determinants can be used to determine the long-term outcomes of 5678 Taiwan Biobank (TWB) participants. GWAS and DNAm analysis revealed RETN variants, rs3219175, rs370006313, and rs3745368, and DNAm sites, cg21271423 and cg09909011, independently associated with circulating resistin levels. Functional assays showed rs370006313 variant played a key role in affecting RETN promoter activity, whereas genotypes of rs3219175 and rs3745368, but not rs370006313, exhibited genome-wide significant associations with RETN promoter DNAm levels. Using Kaplan-Meier survival and Cox regression analyses, participants with progressively increasing resistin levels had a higher hazard ratio for all-cause mortality and cancer mortality compared to those with lower resistin levels. Participants with all three RETN variants (high mutation burden) also exhibited significantly higher hazard ratios for all-cause mortality and cancer mortality, at 3.99 and 5.55, respectively, compared to those without a high mutation burden. In conclusion, RETN rs370006313 is a functional variant affecting RETN promoter activity. Elevated circulating resistin levels and a high RETN mutation burden predict all-cause and cancer mortality in TWB participants. Both resistin levels and RETN variants may serve as biomarkers of long-term outcomes in the general Taiwanese populations. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-cbc0c59036d64ed1821c6e62854626d12025-01-05T12:16:40ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-024-84142-4Circulating resistin levels and mutation burden of the RETN gene variants predict long-term mortality in a Taiwanese populationLung-An Hsu0Ming-Sheng Teng1Semon Wu2Mei-Siou Liao3Hsin-Hua Chou4Yu-Lin Ko5The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University College of MedicineDepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationDepartment of Life Science, Chinese Culture UniversityThe Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationThe Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationDepartment of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationAbstract Human resistin is a proinflammatory cytokine involving the development and progression of cancer and cardiovascular diseases. However, prediction of long-term outcome using circulating resistin level and its genetic determinants in a population-based study remain to be explored. After genome-wide association study (GWAS), DNA methylation (DNAm) analysis and functional assays of a RETN rs370006313 variant, we tested whether resistin level and its genetic determinants can be used to determine the long-term outcomes of 5678 Taiwan Biobank (TWB) participants. GWAS and DNAm analysis revealed RETN variants, rs3219175, rs370006313, and rs3745368, and DNAm sites, cg21271423 and cg09909011, independently associated with circulating resistin levels. Functional assays showed rs370006313 variant played a key role in affecting RETN promoter activity, whereas genotypes of rs3219175 and rs3745368, but not rs370006313, exhibited genome-wide significant associations with RETN promoter DNAm levels. Using Kaplan-Meier survival and Cox regression analyses, participants with progressively increasing resistin levels had a higher hazard ratio for all-cause mortality and cancer mortality compared to those with lower resistin levels. Participants with all three RETN variants (high mutation burden) also exhibited significantly higher hazard ratios for all-cause mortality and cancer mortality, at 3.99 and 5.55, respectively, compared to those without a high mutation burden. In conclusion, RETN rs370006313 is a functional variant affecting RETN promoter activity. Elevated circulating resistin levels and a high RETN mutation burden predict all-cause and cancer mortality in TWB participants. Both resistin levels and RETN variants may serve as biomarkers of long-term outcomes in the general Taiwanese populations.https://doi.org/10.1038/s41598-024-84142-4ResistinRETNGenome-wide association studyDNA methylationMutation burdenLong-term mortality |
| spellingShingle | Lung-An Hsu Ming-Sheng Teng Semon Wu Mei-Siou Liao Hsin-Hua Chou Yu-Lin Ko Circulating resistin levels and mutation burden of the RETN gene variants predict long-term mortality in a Taiwanese population Scientific Reports Resistin RETN Genome-wide association study DNA methylation Mutation burden Long-term mortality |
| title | Circulating resistin levels and mutation burden of the RETN gene variants predict long-term mortality in a Taiwanese population |
| title_full | Circulating resistin levels and mutation burden of the RETN gene variants predict long-term mortality in a Taiwanese population |
| title_fullStr | Circulating resistin levels and mutation burden of the RETN gene variants predict long-term mortality in a Taiwanese population |
| title_full_unstemmed | Circulating resistin levels and mutation burden of the RETN gene variants predict long-term mortality in a Taiwanese population |
| title_short | Circulating resistin levels and mutation burden of the RETN gene variants predict long-term mortality in a Taiwanese population |
| title_sort | circulating resistin levels and mutation burden of the retn gene variants predict long term mortality in a taiwanese population |
| topic | Resistin RETN Genome-wide association study DNA methylation Mutation burden Long-term mortality |
| url | https://doi.org/10.1038/s41598-024-84142-4 |
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