Kaess, Bernhard M. and Tomaszewski, Maciej and Braund, Peter S. and Stark, Klaus and Rafelt, Suzanne and Fischer, Marcus and Hardwick, Robert and Nelson, Christopher P. and Debiec, Radoslaw and Huber, Fritz and Kremer, Werner and Kalbitzer, Hans Robert and Rose, Lynda M. and Chasman, Daniel I. and Hopewell, Jemma and Clarke, Robert and Burton, Paul R. and Tobin, Martin D. and Hengstenberg, Christian and Samani, Nilesh J. (2011) Large-Scale Candidate Gene Analysis of HDL Particle Features. PLOS ONE, 6 (1): e14529. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Background: HDL cholesterol (HDL-C) is an established marker of cardiovascular risk with significant genetic determination. However, HDL particles are not homogenous, and refined HDL phenotyping may improve insight into regulation of HDL metabolism. We therefore assessed HDL particles by NMR spectroscopy and conducted a large-scale candidate gene association analysis. Methodology/Principal Findings: We measured plasma HDL-C and determined mean HDL particle size and particle number by NMR spectroscopy in 2024 individuals from 512 British Caucasian families. Genotypes were 49,094 SNPs in >2,100 cardiometabolic candidate genes/loci as represented on the HumanCVD BeadChip version 2. False discovery rates (FDR) were calculated to account for multiple testing. Analyses on classical HDL-C revealed significant associations (FDR<0.05) only for CETP (cholesteryl ester transfer protein; lead SNP rs3764261: p = 5.6*10(-15)) and SGCD (sarcoglycan delta; rs6877118: p = 8.6*10(-6)). In contrast, analysis with HDL mean particle size yielded additional associations in LIPC (hepatic lipase; rs261332: p = 6.1*10(-9)), PLTP (phospholipid transfer protein, rs4810479: p = 1.7*10(-8)) and FBLN5 (fibulin-5; rs2246416: p = 6.2*10(-6)). The associations of SGCD and Fibulin-5 with HDL particle size could not be replicated in PROCARDIS (n = 3,078) and/or the Women's Genome Health Study (n = 23,170). Conclusions: We show that refined HDL phenotyping by NMR spectroscopy can detect known genes of HDL metabolism better than analyses on HDL-C.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MAGNETIC-RESONANCE-SPECTROSCOPY; CORONARY-ARTERY-DISEASE; MACULAR DEGENERATION; COMMON VARIANTS; BINDING-PROTEIN; SMOOTH-MUSCLE; LIPID-LEVELS; LIPOPROTEIN; FIBULIN-5; LOCI; |
| 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 > Prof. Dr. Dr. Hans Robert Kalbitzer |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Jun 2020 05:42 |
| Last Modified: | 29 Jun 2020 05:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21386 |
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