Genomic, Transcriptomic, and Lipidomic Profiling Highlights the Role of Inflammation in Individuals With Low High-density Lipoprotein Cholesterol
| Autor: | Marjo-Riitta Järvelin, Antti-Pekka Sarin, Johan G. Eriksson, Olli T. Raitakari, Samuli Ripatti, Leena Peltonen, Veikko Salomaa, Sanni Söderlund, Jarkko Soronen, Marja-Riitta Taskinen, Tuulia Hyötyläinen, Johannes Kettunen, Antti Jula, Matej Orešič, Matti Jauhiainen, Jing Tang, Aarno Palotie, Aimo Ruokonen, Christian Ehnholm, Laxman Yetukuri, Terho Lehtimäki, Jussi Naukkarinen, Pirkka-Pekka Laurila, Ida Surakka, Daniel B. Mirel |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Adipose tissue Genome-wide association study Coronary Artery Disease 030204 cardiovascular system & hematology Transcriptome transcriptomics 0302 clinical medicine HLA Antigens Risk Factors Gene Regulatory Networks lipdomics Finland Genetics 0303 health sciences education.field_of_study Genomics Middle Aged HDL-cholesterol Phenotype Adipose Tissue Female lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine coronary artery disease Plasmalogens Quantitative Trait Loci Population Vascular Cell Adhesion Molecule-1 Biology Quantitative trait locus Polymorphism Single Nucleotide Biological pathway 03 medical and health sciences Lipidomics genomics Humans Genetic Predisposition to Disease education 030304 developmental biology Inflammation Gene Expression Profiling Cholesterol HDL nutritional and metabolic diseases ta3121 Health Surveys Logistic Models inflammation Expression quantitative trait loci genome-wide association Linear Models Biomarkers Genome-Wide Association Study |
| Zdroj: | Laurila, P-P, Surakka, I, Sarin, A-P, Yetukuri, L, Hyötyläinen, T, Söderlund, S, Naukkarinen, J, Tang, J, Kettunen, J, Mirel, D B, Soronen, J, Lehtimäki, T, Ruokonen, A, Ehnholm, C, Eriksson, J G, Salomaa, V, Jula, A, Raitakari, O T, Järvelin, M-R, Palotie, A, Peltonen, L, Orešič, M, Jauhiainen, M, Taskinen, M-R & Ripatti, S 2013, ' Genomic, transcriptomic, and lipidomic profiling highlights the role of inflammation in individuals with low high-density lipoprotein cholesterol ', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 33, no. 4, pp. 847-857 . https://doi.org/10.1161/ATVBAHA.112.300733 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Objective— Low high-density lipoprotein cholesterol (HDL-C) is associated with cardiometabolic pathologies. In this study, we investigate the biological pathways and individual genes behind low HDL-C by integrating results from 3 high-throughput data sources: adipose tissue transcriptomics, HDL lipidomics, and dense marker genotypes from Finnish individuals with low or high HDL-C (n=450). Approach and Results— In the pathway analysis of genetic data, we demonstrate that genetic variants within inflammatory pathways were enriched among low HDL-C associated single-nucleotide polymorphisms, and the expression of these pathways upregulated in the adipose tissue of low HDL-C subjects. The lipidomic analysis highlighted the change in HDL particle quality toward putatively more inflammatory and less vasoprotective state in subjects with low HDL-C, as evidenced by their decreased antioxidative plasmalogen contents. We show that the focal point of these inflammatory pathways seems to be the HLA region with its low HDL-associated alleles also associating with more abundant local transcript levels in adipose tissue, increased plasma vascular cell adhesion molecule 1 (VCAM1) levels, and decreased HDL particle plasmalogen contents, markers of adipose tissue inflammation, vascular inflammation, and HDL antioxidative potential, respectively. In a population-based look-up of the inflammatory pathway single-nucleotide polymorphisms in a large Finnish cohorts (n=11 211), no association of the HLA region was detected for HDL-C as quantitative trait, but with extreme HDL-C phenotypes, implying the presence of low or high HDL genes in addition to the population-genomewide association studies–identified HDL genes. Conclusions— Our study highlights the role of inflammation with a genetic component in subjects with low HDL-C and identifies novel cis -expression quantitative trait loci ( cis -eQTL) variants in HLA region to be associated with low HDL-C. |
| Databáze: | OpenAIRE |
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