Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: a preconception and longitudinal cohort studyResearch in context
Summary: Background: Apolipoproteins as an integral part of lipoproteins are crucial for the transport and metabolism of lipids. However, there is a lack of longitudinal studies to quantify the concentrations of maternal apolipoproteins from preconception to postpartum and their associations with m...
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2025-02-01
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| author | Li Chen Karen Mei-Ling Tan Melvin Khee-Shing Leow Kok Hian Tan Jerry Kok Yen Chan Shiao-Yng Chan Yap Seng Chong Peter D. Gluckman Johan G. Eriksson Markus R. Wenk Sartaj Ahmad Mir |
| author_facet | Li Chen Karen Mei-Ling Tan Melvin Khee-Shing Leow Kok Hian Tan Jerry Kok Yen Chan Shiao-Yng Chan Yap Seng Chong Peter D. Gluckman Johan G. Eriksson Markus R. Wenk Sartaj Ahmad Mir |
| author_sort | Li Chen |
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| description | Summary: Background: Apolipoproteins as an integral part of lipoproteins are crucial for the transport and metabolism of lipids. However, there is a lack of longitudinal studies to quantify the concentrations of maternal apolipoproteins from preconception to postpartum and their associations with maternal metabolic health and offspring birth outcomes. Methods: Quantification of apolipoproteins was performed on maternal plasma samples (N = 243 trios) collected at preconception, 26–28 weeks’ pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. Linear regression models and network analysis were implemented to investigate the association of apolipoproteins with maternal genetic variants, biochemical measures, metabolic risk factors, and offspring birth outcomes. Findings: The concentrations of ApoC-III, ApoB and ApoL1 substantially increased in pregnancy compared to preconception and postpartum. Genome-wide association studies (GWAS) identified multiple single-nucleotide polymorphisms (SNPs) associated with plasma apolipoproteins (P < 5.00E-08), including APOE-rs7412 for ApoE, LPA-rs56393506 for Apo(a), APOM-rs707921 for ApoM, ABCC4-rs117797426 for ApoJ, THSD7B-rs575613 for ApoA-II, and LOC102724443-rs140433245 for ApoA-IV. Plasma apolipoproteins were strongly associated with biochemical measures including lipidomic profiles, lipoprotein features and fat-soluble vitamins, as well as metabolic risk factors including glycaemic traits, liver enzymes, inflammatory markers, albumin, and blood pressure. Integrative network analysis of apolipoproteins and their correlates/determinants revealed both shared and specific associations, with the strongest relationships observed among apolipoproteins, cholesterol, triglycerides, alpha tocopherol, and GlycA (Padj < 0.05). Higher maternal ApoC-I and ApoC-III concentrations at preconception were significantly associated with shorter gestational age of the offspring. Interpretation: We describe the longitudinal landscape of maternal circulating apolipoproteins from preconception to postpartum and their associations with maternal metabolic risk factors and offspring birth outcomes. This multi-omics characterisation of biochemical correlates and genetic determinants of maternal apolipoproteins will deepen our understanding of the molecular basis of metabolic flexibility in expectant mothers, leading to better assessment of pregnancy-related outcomes. Funding: This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore- NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. The Singapore Lipidomics Incubator (SLING) is supported by grants from the National University of Singapore via the Life Sciences Institute, the National Research Foundation (NRF, NRFI2015-05 and NRFSBP-P4) and A∗STAR IAF-ICP I1901E0040. Additional funding is provided by Institute for Human Development and Potential (IHDP)—Agency for Science, Technology and Research (A∗STAR), Singapore. |
| format | Article |
| id | doaj-art-f64f1772aa2f4701927cf36a174ff7ca |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-f64f1772aa2f4701927cf36a174ff7ca2025-01-23T05:27:11ZengElsevierEBioMedicine2352-39642025-02-01112105562Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: a preconception and longitudinal cohort studyResearch in contextLi Chen0Karen Mei-Ling Tan1Melvin Khee-Shing Leow2Kok Hian Tan3Jerry Kok Yen Chan4Shiao-Yng Chan5Yap Seng Chong6Peter D. Gluckman7Johan G. Eriksson8Markus R. Wenk9Sartaj Ahmad Mir10Institute for Human Development and Potential, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore; Singapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, Singapore; Co-corresponding author. Institute for Human Development and Potential, Agency for Science, Technology and Research (A∗STAR), 30 Medical Drive, 117609, Singapore.Institute for Human Development and Potential, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore; Department of Laboratory Medicine, National University Hospital, Singapore, SingaporeInstitute for Human Development and Potential, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore; Department of Endocrinology, Tan Tock Seng Hospital, Singapore, Singapore; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; Duke-NUS Medical School, Singapore, Singapore; Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeDuke-NUS Medical School, Singapore, Singapore; KK Women's and Children's Hospital, Singapore, SingaporeDuke-NUS Medical School, Singapore, Singapore; KK Women's and Children's Hospital, Singapore, SingaporeInstitute for Human Development and Potential, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore; Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeInstitute for Human Development and Potential, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore; Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeInstitute for Human Development and Potential, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore; Liggins Institute, University of Auckland, Auckland, New ZealandInstitute for Human Development and Potential, Agency for Science, Technology and Research (A∗STAR), Singapore, Singapore; Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Folkhalsan Research Center, Helsinki, Finland; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, FinlandSingapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, Singapore; College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar; Department of Biochemistry and Precision Medicine Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeSingapore Lipidomics Incubator, Life Sciences Institute, National University of Singapore, Singapore, Singapore; Department of Biochemistry and Precision Medicine Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Corresponding author. Department of Biochemistry and Precision Medicine Translational Research Programme, National University of Singapore, 117596, Singapore.Summary: Background: Apolipoproteins as an integral part of lipoproteins are crucial for the transport and metabolism of lipids. However, there is a lack of longitudinal studies to quantify the concentrations of maternal apolipoproteins from preconception to postpartum and their associations with maternal metabolic health and offspring birth outcomes. Methods: Quantification of apolipoproteins was performed on maternal plasma samples (N = 243 trios) collected at preconception, 26–28 weeks’ pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. Linear regression models and network analysis were implemented to investigate the association of apolipoproteins with maternal genetic variants, biochemical measures, metabolic risk factors, and offspring birth outcomes. Findings: The concentrations of ApoC-III, ApoB and ApoL1 substantially increased in pregnancy compared to preconception and postpartum. Genome-wide association studies (GWAS) identified multiple single-nucleotide polymorphisms (SNPs) associated with plasma apolipoproteins (P < 5.00E-08), including APOE-rs7412 for ApoE, LPA-rs56393506 for Apo(a), APOM-rs707921 for ApoM, ABCC4-rs117797426 for ApoJ, THSD7B-rs575613 for ApoA-II, and LOC102724443-rs140433245 for ApoA-IV. Plasma apolipoproteins were strongly associated with biochemical measures including lipidomic profiles, lipoprotein features and fat-soluble vitamins, as well as metabolic risk factors including glycaemic traits, liver enzymes, inflammatory markers, albumin, and blood pressure. Integrative network analysis of apolipoproteins and their correlates/determinants revealed both shared and specific associations, with the strongest relationships observed among apolipoproteins, cholesterol, triglycerides, alpha tocopherol, and GlycA (Padj < 0.05). Higher maternal ApoC-I and ApoC-III concentrations at preconception were significantly associated with shorter gestational age of the offspring. Interpretation: We describe the longitudinal landscape of maternal circulating apolipoproteins from preconception to postpartum and their associations with maternal metabolic risk factors and offspring birth outcomes. This multi-omics characterisation of biochemical correlates and genetic determinants of maternal apolipoproteins will deepen our understanding of the molecular basis of metabolic flexibility in expectant mothers, leading to better assessment of pregnancy-related outcomes. Funding: This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council (NMRC), Singapore- NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. The Singapore Lipidomics Incubator (SLING) is supported by grants from the National University of Singapore via the Life Sciences Institute, the National Research Foundation (NRF, NRFI2015-05 and NRFSBP-P4) and A∗STAR IAF-ICP I1901E0040. Additional funding is provided by Institute for Human Development and Potential (IHDP)—Agency for Science, Technology and Research (A∗STAR), Singapore.http://www.sciencedirect.com/science/article/pii/S2352396425000064LipoproteinsGWASCardiometabolic healthPregnancyOffspring birth outcomesMulti-omics |
| spellingShingle | Li Chen Karen Mei-Ling Tan Melvin Khee-Shing Leow Kok Hian Tan Jerry Kok Yen Chan Shiao-Yng Chan Yap Seng Chong Peter D. Gluckman Johan G. Eriksson Markus R. Wenk Sartaj Ahmad Mir Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: a preconception and longitudinal cohort studyResearch in context EBioMedicine Lipoproteins GWAS Cardiometabolic health Pregnancy Offspring birth outcomes Multi-omics |
| title | Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: a preconception and longitudinal cohort studyResearch in context |
| title_full | Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: a preconception and longitudinal cohort studyResearch in context |
| title_fullStr | Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: a preconception and longitudinal cohort studyResearch in context |
| title_full_unstemmed | Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: a preconception and longitudinal cohort studyResearch in context |
| title_short | Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: a preconception and longitudinal cohort studyResearch in context |
| title_sort | characterisation of pregnancy induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes a preconception and longitudinal cohort studyresearch in context |
| topic | Lipoproteins GWAS Cardiometabolic health Pregnancy Offspring birth outcomes Multi-omics |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425000064 |
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