Ethnicity-specific skeletal muscle transcriptional signatures and their relevance to insulin resistance in Singapore
Context - Insulin resistance (IR) and obesity differ among ethnic groups in Singapore, with the Malays more obese yet less IR than Asian-Indians. However, the molecular basis underlying these differences is not clear. Objective - As the skeletal muscle (SM) is metabolically relevant to IR, we...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Online Access: | https://hdl.handle.net/10356/147055 |
| _version_ | 1826120719120990208 |
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| author | Tan, Amelia Li Min Langley, Sarah R. Tan, Chee Fan Chai, Jin Fang Khoo, Chin Meng Leow, Melvin Khee-Shing Khoo, Eric Yin Hao Moreno-Moral, Aida Pravenec, Michal Rotival, Maxime Sadananthan, Suresh Anand Velan, S. Sendhil Venkataraman, Kavita Chong, Yap Seng Lee, Yung Seng Sim, Xueling Stunkel, Walter Liu, Mei Hui Tai, E. Shyong Petretto, Enrico |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Tan, Amelia Li Min Langley, Sarah R. Tan, Chee Fan Chai, Jin Fang Khoo, Chin Meng Leow, Melvin Khee-Shing Khoo, Eric Yin Hao Moreno-Moral, Aida Pravenec, Michal Rotival, Maxime Sadananthan, Suresh Anand Velan, S. Sendhil Venkataraman, Kavita Chong, Yap Seng Lee, Yung Seng Sim, Xueling Stunkel, Walter Liu, Mei Hui Tai, E. Shyong Petretto, Enrico |
| author_sort | Tan, Amelia Li Min |
| collection | NTU |
| description | Context -
Insulin resistance (IR) and obesity differ among ethnic groups in Singapore, with the Malays more obese yet less IR than Asian-Indians. However, the molecular basis underlying these differences is not clear.
Objective -
As the skeletal muscle (SM) is metabolically relevant to IR, we investigated molecular pathways in SM that are associated with ethnic differences in IR, obesity, and related traits.
Design, Setting, and Main Outcome Measures -
We integrated transcriptomic, genomic, and phenotypic analyses in 156 healthy subjects representing three major ethnicities in the Singapore Adult Metabolism Study.
Patients -
This study contains Chinese (n = 63), Malay (n = 51), and Asian-Indian (n = 42) men, aged 21 to 40 years, without systemic diseases.
Results -
We found remarkable diversity in the SM transcriptome among the three ethnicities, with >8000 differentially expressed genes (40% of all genes expressed in SM). Comparison with blood transcriptome from a separate Singaporean cohort showed that >95% of SM expression differences among ethnicities were unique to SM. We identified a network of 46 genes that were specifically downregulated in Malays, suggesting dysregulation of components of cellular respiration in SM of Malay individuals. We also report 28 differentially expressed gene clusters, four of which were also enriched for genes that were found in genome-wide association studies of metabolic traits and disease and correlated with variation in IR, obesity, and related traits.
Conclusion -
We identified extensive gene-expression changes in SM among the three Singaporean ethnicities and report specific genes and molecular pathways that might underpin and explain the differences in IR among these ethnic groups. |
| first_indexed | 2024-10-01T05:21:15Z |
| format | Journal Article |
| id | ntu-10356/147055 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:21:15Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1470552021-03-19T06:22:00Z Ethnicity-specific skeletal muscle transcriptional signatures and their relevance to insulin resistance in Singapore Tan, Amelia Li Min Langley, Sarah R. Tan, Chee Fan Chai, Jin Fang Khoo, Chin Meng Leow, Melvin Khee-Shing Khoo, Eric Yin Hao Moreno-Moral, Aida Pravenec, Michal Rotival, Maxime Sadananthan, Suresh Anand Velan, S. Sendhil Venkataraman, Kavita Chong, Yap Seng Lee, Yung Seng Sim, Xueling Stunkel, Walter Liu, Mei Hui Tai, E. Shyong Petretto, Enrico Lee Kong Chian School of Medicine (LKCMedicine) School of Biological Sciences Nanyang Institute of Technology in Health and Medicine Science::Medicine False Discovery Rate Protein-Kinase-C Context - Insulin resistance (IR) and obesity differ among ethnic groups in Singapore, with the Malays more obese yet less IR than Asian-Indians. However, the molecular basis underlying these differences is not clear. Objective - As the skeletal muscle (SM) is metabolically relevant to IR, we investigated molecular pathways in SM that are associated with ethnic differences in IR, obesity, and related traits. Design, Setting, and Main Outcome Measures - We integrated transcriptomic, genomic, and phenotypic analyses in 156 healthy subjects representing three major ethnicities in the Singapore Adult Metabolism Study. Patients - This study contains Chinese (n = 63), Malay (n = 51), and Asian-Indian (n = 42) men, aged 21 to 40 years, without systemic diseases. Results - We found remarkable diversity in the SM transcriptome among the three ethnicities, with >8000 differentially expressed genes (40% of all genes expressed in SM). Comparison with blood transcriptome from a separate Singaporean cohort showed that >95% of SM expression differences among ethnicities were unique to SM. We identified a network of 46 genes that were specifically downregulated in Malays, suggesting dysregulation of components of cellular respiration in SM of Malay individuals. We also report 28 differentially expressed gene clusters, four of which were also enriched for genes that were found in genome-wide association studies of metabolic traits and disease and correlated with variation in IR, obesity, and related traits. Conclusion - We identified extensive gene-expression changes in SM among the three Singaporean ethnicities and report specific genes and molecular pathways that might underpin and explain the differences in IR among these ethnic groups. Agency for Science, Technology and Research (A*STAR) Economic Development Board (EDB) National Medical Research Council (NMRC) This work was funded by the National Medical Research Council Translational Clinical Flagship Research Program (NMRC/TCR/004-NUS/2008) and by the Agency for Science Technology and Research Biomedical Research Council-Economic Development Board Industry Alignment Fund Category 3 Fund (IAF311002). E.S.T. is supported by a Clinician Scientist Award (NMRC/CSA-SI/0002/ 2015) and M.H.L. by an open-fund young individual research grant (NMRC/BNIG/2027/2015) from the National Medical Research Council. M.P. was supported by Grant 14-36804G from the Czech Science Foundation. 2021-03-19T06:22:00Z 2021-03-19T06:22:00Z 2019 Journal Article Tan, A. L. M., Langley, S. R., Tan, C. F., Chai, J. F., Khoo, C. M., Leow, M. K., Khoo, E. Y. H., Moreno-Moral, A., Pravenec, M., Rotival, M., Sadananthan, S. A., Velan, S. S., Venkataraman, K., Chong, Y. S., Lee, Y. S., Sim, X., Stunkel, W., Liu, M. H., Tai, E. S. & Petretto, E. (2019). Ethnicity-specific skeletal muscle transcriptional signatures and their relevance to insulin resistance in Singapore. The Journal of Clinical Endocrinology & Metabolism, 104(2), 465-486. https://dx.doi.org/10.1210/jc.2018-00309 0021-972X https://hdl.handle.net/10356/147055 10.1210/jc.2018-00309 30137523 2-s2.0-85059280821 2 104 465 486 en NMRC/TCR/004-NUS/2008 IAF311002 NMRC/CSA-SI/0002 NMRC/BNIG/2027/2015 The Journal of Clinical Endocrinology & Metabolism © 2019 Endocrine Society. All rights reserved. |
| spellingShingle | Science::Medicine False Discovery Rate Protein-Kinase-C Tan, Amelia Li Min Langley, Sarah R. Tan, Chee Fan Chai, Jin Fang Khoo, Chin Meng Leow, Melvin Khee-Shing Khoo, Eric Yin Hao Moreno-Moral, Aida Pravenec, Michal Rotival, Maxime Sadananthan, Suresh Anand Velan, S. Sendhil Venkataraman, Kavita Chong, Yap Seng Lee, Yung Seng Sim, Xueling Stunkel, Walter Liu, Mei Hui Tai, E. Shyong Petretto, Enrico Ethnicity-specific skeletal muscle transcriptional signatures and their relevance to insulin resistance in Singapore |
| title | Ethnicity-specific skeletal muscle transcriptional signatures and their relevance to insulin resistance in Singapore |
| title_full | Ethnicity-specific skeletal muscle transcriptional signatures and their relevance to insulin resistance in Singapore |
| title_fullStr | Ethnicity-specific skeletal muscle transcriptional signatures and their relevance to insulin resistance in Singapore |
| title_full_unstemmed | Ethnicity-specific skeletal muscle transcriptional signatures and their relevance to insulin resistance in Singapore |
| title_short | Ethnicity-specific skeletal muscle transcriptional signatures and their relevance to insulin resistance in Singapore |
| title_sort | ethnicity specific skeletal muscle transcriptional signatures and their relevance to insulin resistance in singapore |
| topic | Science::Medicine False Discovery Rate Protein-Kinase-C |
| url | https://hdl.handle.net/10356/147055 |
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