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Knjižnica je med tednom odprta od 8. do 19. ure, ob sobotah od 9. do 13. ure. Čitalnica ČUK je odprta od ponedeljka do sobote od 9. do 24. ure, ob nedeljah od 16. do 24. ure. Informacije: 02 25 07 431, ukm@um.si
  • Stratégies de médecine personnalisée pour l'étude et l'utilisation de nouveaux biomarqueurs : thèse
    Gorenjak, Vesna, 1991-
    The fight against common chronic diseases, which are characterised by complex mechanisms of molecular regulation, requires the implementation of new risk prediction and prevention strategies. ... Personalised medicine offers sophisticated approaches for successful management of the morbidities of the ageing population. In this thesis, inspired by the principles of personalised medicine, we describe an integrative approach combining "-omics" methodologies. We use a model of a "common denominator" for cardiovascular disease (CVD) and other chronic diseases to identify biomarkers linked with common diseases risk factors and molecular pathways. The results of this work are presented in five original publications, three review articles, and one publication under redaction. All publications aim to strengthen and facilitate the implementation of personalised medicine in healthcare. The three main biomarkers of our interest are triggering receptors expressed on myeloid cells (TREM2), vascular endothelial growth factor A (VEGF-A) and telomere length (TL) and are studied mainly in the supposed healthy population of the STANISLAS Family Study. With the investigation of genetic variants, located in the region of the TREM2 gene, we identified the association of the SNP rs6918289 with increased levels of TNF-% and intimamedia thickness of the femoral artery (IMT-F). As inflammation and increased IMT-F are important indicators of the formation of the atherosclerotic plaque, the minor allele (T) of rs6918289 might be considered a risk allele for inflammatory diseases and atherosclerosis. With the use of an epigenome-wide association studies (EWAS), we identified novel epigenetic biomarkers, related to common diseases risk factors: central obesity and increased lipid levels. One methylation site (CpG) was associated with increased waist circumference (WC) (cg16170243), which could explain the epigenetic regulation of central obesity via increased insulin resistance. Moreover, an EWAS of the triglyceride (TG) levels identified two significant CpG sites, one of which was replicated in the adipose tissue (cg04580029), giving insights into epigenetic regulation of lipid levels. The results of these two last studies provided new epigenetic biomarkers and might contribute to future diagnostics and therapeutic interventions. An EWAS was also used to study the epigenetic regulation of VEGF-A concentrations; 20 CpG sites were identified, and their relations with VEGF-A were analysed through detailed bioinformatics analysis. Methylation of genes, such as TPX2 and HAS, could affect their activity and would in turn cause increased VEGF-A concentrations. VEGF-A was further investigated for its relation with 11 cytokines, important mediators of common physiological pathways of the majority of chronic diseases. VEGF-A protein levels were associated with IL-4, MCP1 and EGF. Specific VEGF-A mRNA isoforms were also investigated for their association with cytokines; VEGF165 showed significant associations with MCP1 and IL-1% and VEGF189 with IL-4 and IL-6. Together with another important biomarker, TL, we studied the role of VEGF-A in atherosclerosis, and we identified one VEGF-A related genetic variant significantly associated with telomere attrition (calculated as a ratio between leukocyte TL and muscular TL). This genetic variant could present a common denominator of chronic diseases. In conclusion, the employment of diverse methodologies for the investigation of common chronic diseases risk factors and pathways provided new diagnostic markers and generated results, which could help to improve the diseases risk prediction based on the individual genetic "make-up". New insights into associations between different biomarkers might help in understanding the (patho) physiological pathways common between CVDs and other chronic diseases. Finally, we hope that the results of this thesis through close collaboration with industry will facilitate the implementation of personalised healthcare.
    Vrsta gradiva - disertacija ; neleposlovje za odrasle
    Založništvo in izdelava - Nancy : V. Gorenjak, 2019
    Jezik - francoski
    COBISS.SI-ID - 65640195

    Povezava(-e):

    http://docnum.univ-lorraine.fr/public/DDOC_T_2019_0106_GORENJAK.pdf

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