Disclosure: The authors declared no conflict of interest.
Genetic predisposition to an adverse lipid profile limits the improvement in total cholesterol in response to weight loss
Article first published online: 29 MAY 2013
Copyright © 2013 The Obesity Society
Volume 21, Issue 12, pages 2589–2595, December 2013
How to Cite
Walker, C. G., Holzapfel, C., Loos, R. J.F., Mander, A. P., Klopp, N., Illig, T., Caterson, I. D., Hauner, H. and Jebb, S. A. (2013), Genetic predisposition to an adverse lipid profile limits the improvement in total cholesterol in response to weight loss. Obesity, 21: 2589–2595. doi: 10.1002/oby.20328
Funding agencies: This study was funded by the participating centers including UK Medical Research Council (grant codes U105960389, U1052.00.014). The intervention trial was funded by Weight Watchers International through a grant to the UK Medical Research Council. SAJ, HH and IDC declare financial support to their institutions for the original trial from Weight Watchers, including a stipend supporting CH. SAJ has received research grants for other clinical trials from Sanofi-Aventis and Coca Cola. IDC has received research grants for other clinical trials funded by Sanofi-Aventis, Allergan, Roche Products, MSD, and GlaxoSmithKline. HH has received a travel grant from Roche. SAJ is a member of the Tanita Medical Advisory Board and has received payment for nutrition articles and lectures for Rosemary Conley Enterprises. HH is on the Advisory Board for Weight Watchers International and has received payment for lectures from Sara Lee, Lilly, Novartis, Sanofi-Aventis, and Bristol-Myers Squibb. IDC was a board member for the SCOUT trial and has received payment for lectures from iNova Pharmaceuticals, Eisai Pharmaceuticals, Pfizer Australia, and Servier Laboratories (Australia). CGW, RJFL, APM, TI & NK declare no conflict of interest.
- Issue published online: 3 DEC 2013
- Article first published online: 29 MAY 2013
- Accepted manuscript online: 18 FEB 2013 12:13AM EST
- Manuscript Accepted: 7 DEC 2012
- Manuscript Received: 10 AUG 2012
- participating centers including UK Medical Research Council. Grant Numbers: U105960389, U1052.00.014
- Weight Watchers International through a grant to the UK Medical Research Council
- IDC has received research grants for other clinical trials funded by Sanofi-Aventis, Allergan, Roche Products, MSD, and GlaxoSmithKline
- Tanita Medical Advisory Board and has received payment for nutrition articles and lectures for Rosemary Conley Enterprises
- HH is on the Advisory Board for Weight Watchers International
- SCOUT trial and has received payment for lectures from iNova Pharmaceuticals
Overweight and obesity are associated with a dyslipidaemia which can be improved by weight loss. Whether genetic predisposition to an adverse lipid profile modifies such beneficial effects of weight loss on lipid levels in overweight and obese individuals was examined.
Design and methods
White European participants (n = 374) who completed a 12-month weight loss trial were genotyped for 36 lipid-associated single nucleotide polymorphisms (SNPs), previously identified in genome-wide association studies (GWAS). Genetic predisposition scores (GPSs) were calculated for four lipid traits by summing the number of risk alleles (RA) for each participant. The associations of each GPS with four lipid traits were assessed at baseline, and with lipid changes in response to weight change after 12 months.
At baseline, the trait-specific GPSs were associated with 0.11 ± 0.04 mM higher total cholesterol/RA (P = 0.004), 0.05 ± 0.02 mM higher low density lipoprotein cholesterol/RA (P = 0.005), 0.03 ± 0.007 mM lower high density lipoprotein cholesterol/RA (P = 0.00002) and 0.04 ± 0.01 mM higher triglyceride/RA (P = 0.00002). After the intervention, weight loss was associated with improvements in all lipids (P < 0.01). GPS attenuated the weight loss-associated reduction in TC so those with a higher GPS had less improvement (interaction = 0.01 ± 0.005 mM/GPS/kg weight loss, P = 0.003). A similar pattern was observed for LDLC (interaction = 0.004 ± 0.002 mM/GPS/kg weight loss, P = 0.07). There was no evidence of a GPS-modifying effect for change in HDLC or TG.
Genetic predisposition is an important determinant of lipid levels and appears to limit the improvement in TC and to some extent LDLC levels, but not in other plasma lipids, in response to weight loss. © 2013 American Institute of Chemical Engineers AIChE J, 2013