دورية أكاديمية
Altered blood gene expression in the obesity-related type 2 diabetes cluster may be causally involved in lipid metabolism: a Mendelian randomisation study.
| العنوان: | Altered blood gene expression in the obesity-related type 2 diabetes cluster may be causally involved in lipid metabolism: a Mendelian randomisation study. |
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| المؤلفون: | de Klerk JA; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, the Netherlands., Beulens JWJ; Amsterdam Public Health Institute, Amsterdam UMC, Amsterdam, the Netherlands.; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.; Department of Epidemiology and Data Science, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands., Mei H; Sequencing Analysis Support Core, Leiden University Medical Center, Leiden, the Netherlands., Bijkerk R; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, the Netherlands., van Zonneveld AJ; Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, the Netherlands., Koivula RW; Department of Clinical Sciences, Lund University, Genetic and Molecular Epidemiology, CRC, Skåne University Hospital Malmö, Malmö, Sweden., Elders PJM; Amsterdam Public Health Institute, Amsterdam UMC, Amsterdam, the Netherlands.; Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands., 't Hart LM; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.; Amsterdam Public Health Institute, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Epidemiology and Data Science, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands.; Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands., Slieker RC; Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands. r.c.slieker@lumc.nl.; Amsterdam Public Health Institute, Amsterdam UMC, Amsterdam, the Netherlands. r.c.slieker@lumc.nl.; Department of Epidemiology and Data Science, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands. r.c.slieker@lumc.nl. |
| المصدر: | Diabetologia [Diabetologia] 2023 Jun; Vol. 66 (6), pp. 1057-1070. Date of Electronic Publication: 2023 Feb 24. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0006777 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0428 (Electronic) Linking ISSN: 0012186X NLM ISO Abbreviation: Diabetologia Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Berlin Springer Verlag |
| مواضيع طبية MeSH: | Diabetes Mellitus, Type 2*/genetics , RNA, Long Noncoding*/genetics , RNA, Long Noncoding*/metabolism , Insulins*, Humans ; Lipid Metabolism/genetics ; Genome-Wide Association Study ; Cholesterol, HDL ; Gene Expression ; Obesity/complications ; Obesity/genetics ; Receptors, Peptide/genetics ; Receptors, Peptide/metabolism ; Receptors, G-Protein-Coupled/metabolism |
| مستخلص: | Aims/hypothesis: The aim of this study was to identify differentially expressed long non-coding RNAs (lncRNAs) and mRNAs in whole blood of people with type 2 diabetes across five different clusters: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), mild diabetes (MD) and mild diabetes with high HDL-cholesterol (MDH). This was to increase our understanding of different molecular mechanisms underlying the five putative clusters of type 2 diabetes. Methods: Participants in the Hoorn Diabetes Care System (DCS) cohort were clustered based on age, BMI, HbA Results: Eleven lncRNAs and 175 mRNAs were differentially expressed in the MOD cluster, the lncRNA AL354696.2 was upregulated in the SIDD cluster and GPR15 mRNA was downregulated in the MDH cluster. mRNAs and lncRNAs that were differentially expressed in the MOD cluster were correlated among each other. Six lncRNAs and 120 mRNAs validated in the IMI DIRECT study. Using two-sample Mendelian randomisation, we found 52 mRNAs to have a causal effect on anthropometric traits (n=23) and lipid metabolism traits (n=10). GPR146 showed a causal effect on plasma HDL-cholesterol levels (p = 2×10 -15 ), without evidence for reverse causality. Conclusions/interpretation: Multiple lncRNAs and mRNAs were found to be differentially expressed among clusters and particularly in the MOD cluster. mRNAs in the MOD cluster showed a possible causal effect on anthropometric traits, lipid metabolism traits and blood cell fractions. Together, our results show that individuals in the MOD cluster show aberrant RNA expression of genes that have a suggested causal role on multiple diabetes-relevant traits. (© 2023. The Author(s).) |
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| فهرسة مساهمة: | Keywords: Clusters; Lipid metabolism; Long non-coding RNA; Obesity; Two-sample Mendelian randomisation; Type 2 diabetes |
| المشرفين على المادة: | 0 (RNA, Long Noncoding) 0 (Cholesterol, HDL) 0 (Insulins) 0 (GPR15 protein, human) 0 (Receptors, Peptide) 0 (Receptors, G-Protein-Coupled) |
| تواريخ الأحداث: | Date Created: 20230224 Date Completed: 20230508 Latest Revision: 20230523 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC10163084 |
| DOI: | 10.1007/s00125-023-05886-8 |
| PMID: | 36826505 |
| قاعدة البيانات: | MEDLINE |
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| DOI: | 10.1007/s00125-023-05886-8 |