Zusammenfassung
Moderne Methoden der Genexpressionsanalyse erlauben es, alle Transkripte, also das gesamte Transkriptom einer Zelle oder eines Gewebes, simultan zu untersuchen. Derzeit können mit DNA-Microarray-Techniken Transkriptspiegel zu fast allen proteinkodierenden Genen im Genom gemessen werden. Sequenzierbasierte Ansätzen ermöglichen eine noch vollständigere Erfassung, da mit ihnen alle Sequenzen der exprimierten Transkripte bestimmt und somit auch unbekannte und nichtproteinkodierende RNAs identifiziert werden können. Erste Querschnittsstudien zur Genexpression in Skelettmuskel, Leber, Fett und Blut haben gezeigt, dass Genexpressionsprofile in diesen Geweben mit Insulinresistenz und Diabetes korrelieren. Untersuchungen im bevölkerungsbasierten KORA-Survey F4 belegten insbesondere Assoziationen zwischen mRNA-Transkripten im Vollblut und 2-h-Glukosespiegeln aus dem oGTT. Ob RNA-Transkripte helfen, Hochrisikopersonen frühzeitig zu erkennen und klinisch relevante Unterformen des Typ-2-Diabetes aufzudecken, muss in prospektiven Studien untersucht werden. Ebenso ist noch unbekannt, ob die Kombinationen von Biomarkern aus verschiedenen „Omics“-Technologien unser Verständnis der Entwicklung des Typ-2-Diabetes verbessern kann.
Abstract
Modern methods of gene expression analysis allow the simultaneous characterization of all transcripts, i.e. the entire transcriptome of a cell or tissue. Current DNA microarray-based technologies are able to quantify transcript levels of almost all protein coding genes in the genome. Sequencing-based approaches enable an even more complete investigation, because they provide all sequences of expressed transcripts including previously unknown and non-protein coding RNAs. Cross-sectional studies on gene expression in skeletal muscle, liver, adipose tissue and blood have demonstrated that gene expression profiles in these tissues correlate with insulin resistance and diabetes. Analyses in the population-based KORA survey F4 revealed that mRNA transcripts in whole blood were especially associated with 2 h glucose levels in the oral glucose tolerance test (OGTT). Prospective studies will have to show whether RNA transcripts can help in the early identification of high-risk individuals and in the definition of novel clinically relevant subtypes of type 2 diabetes. Also it remains to be seen whether the combination of biomarkers from different “omics” technologies can give further insight into the development of type 2 diabetes.
Literatur
Aziz H, Zaas A, Ginsburg GS (2007) Peripheral blood gene expression profiling for cardiovascular disease risk assessment. Genomic Med 1:105–112
Buijsse B, Simmons RK, Griffin SJ et al (2011) Risk assessment tools for identifying individuals at risk of developing type 2 diabetes. Epidemiol Rev 33:46–62
Carstensen M, Herder C, Kivimäki M et al (2010) Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study. Diabetes 59:1222–1227
Elbein SC, Kern PA, Rasouli N et al (2011) Global gene expression profiles of subcutaneous adipose and muscle from glucose-tolerant, insulin-sensitive, and insulin-resistant individuals matched for BMI. Diabetes 60:1019–1029
Fernandez-Valverde SL, Taft RJ, Mattick JS (2011) MicroRNAs in beta-cell biology, insulin resistance, diabetes and ist complications. Diabetes 60:1825–1831
Frederiksen CM, Hojlund K, Hansen L et al (2008) Transcriptional profiling of myotubes from patients with type 2 diabetes: no evidence for a primary defect in oxidative phosphorylation genes. Diabetologia 51:2068–2077
Gallagher IJ, Scheele C, Keller P et al (2010) Integration of microRNA changes in vivo identifies novel molecular features of muscle insulin resistance in type 2 diabetes. Genome Med 2:9
Herder C, Carstensen M, Landwehr S et al (2011) Genome-wide associations between gene expression in peripheral blood and fasting and 2-hour glucose levels in the population-based KORA Survey F4. Diabetologia 54 (Suppl 2):S 75 (abstract)
Herder C, Karakas M, Koenig W (2011) Biomarkers for the prediction of type 2 diabetes and cardiovascular disease. Clin Pharmacol Ther 90:52–66
Herder C, Roden M (2010) Genetische Studien zum Typ 2 Diabetes. Mögliche Implikationen für Prävention und Therapie. Diabetologe 6:203–209
Herder C, Roden M (2011) Genetics of type 2 diabetes: pathophysiological and clinical relevance. Eur J Clin Invest 41:679–692
Metzker ML (2010) Sequencing technologies – the next generation. Nat Rev Genet 11:31–46
Mootha VK, Lindgren CM, Eriksson KF et al (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34:267–273
Ozsolak F, Platt AR, Jones DR et al (2009) Direct RNA sequencing. Nature 461:814–818
Patti ME, Butte AJ, Crunkhorn S et al (2003) Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A 100:8466–8471
Rathmann W, Kowall B, Heier M et al (2010) Prediction models for incident type 2 diabetes mellitus in the older population: KORA S 4/F4 cohort study. Diabet Med 27:1116–1123
Sattar N, McConnachie A, Ford I et al (2007) Serial measurements and conversion to type 2 diabetes in the West of Scotland Coronary Prevention Study: specific elevations in alanine aminotransferase and triglycerides suggest hepatic fat accumulation as a potential contributing factor. Diabetes 56:984–991
Sinnaeve PR, Donahue MP, Grass P et al (2009) Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease. PLoS One 4:e7037
Tabák AG, Jokela M, Akbaraly TN et al (2009) Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 373:2215–2221
Takamura T, Honda M, Sakai Y et al (2007) Gene expression profiles in peripheral blood mononuclear cells reflect the pathophysiology of type 2 diabetes. Biochem Biophys Res Commun 361:379–384
Wang ET, Sandberg R, Luo S et al (2008) Alternative isoform regulation in human tissue transcriptomes. Nature 456:470–476
Wingrove JA, Daniels SE, Sehnert AJ et al (2008) Correlation of peripheral-blood gene expression with the extent of coronary artery stenosis. Circ Cardiovasc Genet 1:31–38
Zampetaki A, Kiechl S, Drozdov I et al (2010) Plasma microRNA profiling reveals loss of endothelial MiR-126 and other microRNAs in type 2 diabetes. Circ Res 107:810–817
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Herder, C., Roden, M., Carstensen, M. et al. Transcriptomics und Typ-2-Diabetes. Diabetologe 8, 35–41 (2012). https://doi.org/10.1007/s11428-011-0777-x
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DOI: https://doi.org/10.1007/s11428-011-0777-x