Heikki Koistinen, M.D., Dr.Med.Sci., Docent, Head
Selina Mäkinen, M.Sc.
Leena Kinnunen, Phil. kand.

In 2014, the primary focus of research activity in the group was on the regulation of glucose and fatty acid metabolism in skeletal muscle. To this end, the team established a collection of primary human muscle cells from clinically characterized subjects from different glucose tolerance phenotypes, including normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (T2D). A variety of biochemical and functional analyses with these collections are currently ongoing.

In FUSION (Finnish United States Investigation on NIDDM Genetics) Tissue Biopsy study we collected muscle, adipose and skin samples from a cohort of >300 clinically characterized Finnish people across all glucose tolerance stages. Sampling was performed in 2009–2013. Analysis of the skeletal muscle transcriptome by RNA sequencing of vastus lateralis muscle biopsies from 279 subjects was completed in 2014. With these patient materials, we performed dense genotyping and imputation, as well as constructed and sequenced strand-specific mRNAseq libraries. Using expression quantitative trait loci (eQTL), we identified >8000 genes, some of which appear to be disease-state specific. Multiple eQTLs are in high linkage disequilibrium with genomewide association studies single nucleotide polymorphisms for T2D, pinpointing genes as candidates for a role in T2D risk. Further analyses of FUSION Tissue Biopsy samples are currently ongoing.

Figure. Human myotubes after seven days of differentiation. For immunocytochemistry, cells were stained with DNA binding dye DAPI to show nuclei (blue) and muscle-specific antibody desmin (red) to show the myotubes. The photograph was taken at 20X magnification using a Leica fluorescence microscope.

As a part of a large international collaboration, whole-exome sequencing data from peripheral blood DNA of >17,000 persons was analysed. The presence of detectable somatic mutations rose in frequency with advancing age, with prevalence being highest in age group of people >90 years of age. The highest proportion of somatic mutations occurred in three genes: DNMT3A, TET2, and ASXL1, and the presence of a variant increased not only the risk of hematological malignancy, but increased allcause mortality and the risk of cardiovascular disease, as well.

Contact info

Heikki Koistinen, MD, PhD, Docent

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