Petersen, Ann-Kristin and Stark, Klaus and Musameh, Muntaser D. and Nelson, Christopher P. and Roemisch-Margl, Werner and Kremer, Werner and Raffler, Johannes and Krug, Susanne and Skurk, Thomas and Rist, Manuela J. and Daniel, Hannelore and Hauner, Hans and Adamski, Jerzy and Tomaszewski, Maciej and Doering, Angela and Peters, Annette and Wichmann, H-Erich and Kaess, Bernhard M. and Kalbitzer, Hans Robert and Huber, Fritz and Pfahlert, Volker and Samani, Nilesh J. and Kronenberg, Florian and Dieplinger, Hans and Illig, Thomas and Hengstenberg, Christian and Suhre, Karsten and Gieger, Christian and Kastenmueller, Gabi (2012) Genetic associations with lipoprotein subfractions provide information on their biological nature. HUMAN MOLECULAR GENETICS, 21 (6). pp. 1433-1443. ISSN 0964-6906,
Full text not available from this repository. (Request a copy)Abstract
Adverse levels of lipoproteins are highly heritable and constitute risk factors for cardiovascular outcomes. Hitherto, genome-wide association studies revealed 95 lipid-associated loci. However, due to the small effect sizes of these associations large sample numbers (100 000 samples) were needed. Here we show that analyzing more refined lipid phenotypes, namely lipoprotein subfractions, can increase the number of significantly associated loci compared with bulk high-density lipoprotein and low-density lipoprotein analysis in a study with identical sample numbers. Moreover, lipoprotein subfractions provide novel insight into the human lipid metabolism. We measured 15 lipoprotein subfractions (L1L15) in 1791 samples using H-1-NMR (nuclear magnetic resonance) spectroscopy. Using cluster analyses, we quantified inter-relationships among lipoprotein subfractions. Additionally, we analyzed associations with subfractions at known lipid loci. We identified five distinct groups of subfractions: one (L1) was only marginally captured by serum lipids and therefore extends our knowledge of lipoprotein biochemistry. During a lipid-tolerance test, L1 lost its special position. In the association analysis, we found that eight loci (LIPC, CETP, PLTP, FADS1-2-3, SORT1, GCKR, APOB, APOA1) were associated with the subfractions, whereas only four loci (CETP, SORT1, GCKR, APOA1) were associated with serum lipids. For LIPC, we observed a 10-fold increase in the variance explained by our regression models. In conclusion, NMR-based fine mapping of lipoprotein subfractions provides novel information on their biological nature and strengthens the associations with genetic loci. Future clinical studies are now needed to investigate their biomedical relevance.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CORONARY-ARTERY-DISEASE; HEART-DISEASE; HDL CHOLESTEROL; RISK; METABOLISM; PLASMA; LIPIDS; SERUM; ATHEROSCLEROSIS; HETEROGENEITY; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Dr. Hans Robert Kalbitzer |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 May 2020 10:55 |
| Last Modified: | 18 May 2020 10:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19053 |
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