Biology subjects

Taskinen, M.-R.

Publications and source records attributed to Taskinen, M.-R..

4 recordsLinked to original sources

bioRxiv2023

Multi-omics characterization of lymphedema-induced adipose tissue from breast cancer patients

ObjectiveSecondary lymphedema (LE) following breast cancer surgery is a life-long complication, which currently has no cure. LE induces significant regional adipose tissue deposition, requiring liposuction as a treatment. Here, we aimed to elucidate the transcriptional, metabolomic, and lipidomic signature of the adipose tissue developed due to the surgery-induced LE in short- and long-term LE patients, and compared the transcriptomic landscape in LE to the obesity-induced adipose tissue. MethodsAdipose tissue biopsies were obtained from breast cancer-operated females with LE from the affected and non-affected arms (n=20 patients). To decipher molecular properties of the LE adipose tissue, we performed RNA sequencing, metabolomics, and lipidomics combined with bioinformatics analyses. ResultsIntegrative analysis of functional genomics revealed that inflammatory response, cell chemotaxis and angiogenesis were upregulated biological processes in the LE arm, indicating a sustained inflammation in the edematous adipose tissue, whereas, epidermal differentiation, cell-cell junction organization, water homeostasis and neurogenesis were, in turn, downregulated in the LE arm. Surprisingly, only few genes were found to be the same in the LE-induced and the obesity-induced adipose tissue expansion, indicating a different type of adipose tissue development in these two diseases. In metabolomics analysis, the concentration of a branched-chain amino acid valine was found to be reduced in the edematous arm together with downregulation of mRNA levels of its transporter SLC6A15. Lipidomics analyses did not show any significant differences between the diseased and healthy arm, suggesting that diet affects the lipid composition of the adipose tissue more than the LE. ConclusionsOur results provide a detailed molecular characterization of adipose tissue in secondary LE of breast cancer patients vs individuals with obesity. The results show distinct differences in transcriptomic signatures between LE patients vs individuals with obesity, but only minor differences in metabolome and lipidome between the diseased and the healthy arm.

pathology↗

bioRxiv2019

Polygenic Hyperlipidemias and Coronary Artery Disease Risk

BackgroundHyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). Monogenic familial hypercholesterolemia associates with higher increase in CAD risk than expected from a single LDL-C measurement, likely due to lifelong cumulative exposure to high LDL-C. It remains unclear to what extent a high polygenic load of LDL-C or TG-increasing variants associates with increased CAD risk.\n\nMethods and ResultsWe derived polygenic risk scores (PRS) with [~]6M variants for LDL-C and TG with weights from a UK biobank-based genome-wide association study with [~]500K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the FINRISK cohort, and to CAD risk in 135 300 individuals (13 695 CAD cases) from the FinnGen project.\n\nIn FINRISK, LDL-C ranged from 2.83 (95% CI 2.79-2.89) to 3.80 (3.72-3.88) and TG from 0.99 (0.95-1.01) to 1.52 (1.48-1.58) mmol/l between the lowest and highest 5% of the respective PRS distributions. The corresponding CAD prevalences ranged from 8.2% to 12.7% for the LDL-C PRS and from 8.2% to 12.1% for the TG PRS in FinnGen. Furthermore, CAD risk was 1.36-fold higher (OR, 95% CI 1.24-1.49) for the LDL-C PRS and 1.31-fold higher (1.20-1.44) for the TG PRS for those with the PRS >95th percentile vs those without. These estimates were only slightly attenuated when adjusting for a CAD PRS (OR 1.26 [95% CI 1.15-1.39] for LDL-C and 1.21 [1.10-1.32] for TG PRS).\n\nConclusionsThe CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and mostly independent of a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing more direct guidance for clinical translation.

genomics↗

bioRxiv2018

Genetics of human plasma lipidome: Understanding lipid metabolism and its link to diseases beyond traditional lipids

AimGenetic investigation of human plasma lipidome to get insights into lipid-related disorders beyond traditional lipid measures.\n\nMethods and ResultsWe performed a genome-wide association study (GWAS) of 141 lipid species (n=2,181 individuals), followed by phenome-wide scans (PheWAS) with 44 clinical endpoints related to cardiometabolic, psychiatric and gastrointestinal disorders (n=456,941 individuals). SNP-based heritability for lipid species ranged from 0.10-0.54. Lipids with long-chain polyunsaturated fatty acids showed higher heritability and genetic sharing, suggesting considerable genetic regulation at acyl chains levels. We identified 35 genomic regions associated with at least one lipid species (P<5x10-8), revealing 37 new SNP-lipid species pair associations e.g. new association between ABCG5/8 and CE(20:2;0). PheWAS of lipid-species-associated loci suggested new associations of BLK with obesity, FADS2 with thrombophlebitis, and BLK and SPTLC3 with gallbladder disease (false discovery rate <0.05). The association patterns of lipid-species-associated loci supplied clues to their probable roles in lipid metabolism e.g. suggestive role of SYNGR1, MIR100HG, and PTPRN2 in desaturation and/or elongation of fatty acids. At known lipid loci (FADS2, APOA5 and LPL), genetic associations provided detailed insights to their roles in lipid biology and diseases. We also show that traditional lipid measures may fail to capture lipids such as lysophospatidylcholines (LPCs) and phosphatidylcholines (PCs) that are potential disease risk factors, but are not included in routine screens. The full genome-wide association statistics are available on the web-based database (http://35.205.141.92).\n\nConclusionOur study reveals genetic regulation of plasma lipidome and highlights the potential of lipidomic profiling in disease gene mapping.

genetics↗

bioRxiv2018

Coronary artery disease risk and lipidomic profiles are similar in familial and population-ascertained hyperlipidemias

Aims: To characterize and compare coronary artery disease (CAD) risk and detailed lipidomic profiles of individuals with familial and population-ascertained hyperlipidemias.\n\nMethods and Results: We determined incident CAD risk for 760 members of 66 hyperlipidemic families ([≥] 2 first degree relatives with the same hyperlipidemia) and 19,644 Finnish FINRISK population study participants. We also quantified 151 lipid species in plasma or serum samples from 550 members of 73 hyperlipidemic pedigrees and 897 FINRISK participants using a mass spectrometric shotgun lipidomics platform. Hyperlipidemias (LDL-C or triacylglycerides over 90th population percentile) were associated with increased CAD risk (high LDL-C: HR 1.74, 95% CI 1.48-2.04; high triacylglycerides: HR 1.38, 95% CI 1.09-1.74) and the risk estimates were very similar between the family and population samples. High LDL-C was associated with altered levels of 105 lipid species in families (p-value range 0.033-7.3*10-20 at 5% false discovery rate) and 51 species in the population samples (p-value range 0.017-6.8*10-21). Hypertriglyceridemia was associated with altered levels of 117 lipid species in families (p-value range 0.035-1.8*10-49) and 119 species in the population sample (p-value range 0.038-2.3*10-56). The lipidomics profiles of hyperlipidemias were highly similar in families and population samples.\n\nConclusion: We identified distinct lipidomic profiles associated with high LDL-C and triacylglyceride levels. CAD risk, lipidomic profiles and genetic profiles are highly similar between familial and population-ascertained hyperlipidemias, providing evidence of similar and overlapping underlying mechanisms. Our results do not support different screening and treatment for such hyperlipidemias.

epidemiology↗