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- Title
Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program.
- Authors
Pollin, Toni I.; Isakova, Tamara; Jablonski, Kathleen A.; De Bakker, Paul I. W.; Taylor, Andrew; Mcateer, Jarred; Qing Pan; Horton, Edward S.; Delahanty, Linda M.; Altshuler, David; Shuldiner, Alan R.; Goldberg, Ronald B.; Florez, Jose C.; Franks, Paul W.
- Abstract
Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04-161017). Except for total HDL particles (r =20.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07-0.17, P =5x10 5-1x1019). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (Β= +0.87, SEE±0.22 mg/dl/allele, P =8x10-5 , Pinteraction = 0.02) in the lifestyle intervention group, but not in the placebo (Β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (Β =20.03, SEE±0.22 mg/dl/allele, P = 0.90; Pinteraction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (Β = +0.30, SEE±0.012 ln nmol/L/ allele, P = 0.01, Pinteraction = 0.01) but not in the placebo (Β =-0.002, SEEx0.008 ln nmol/L/allele, P = 0.74) or metformin (Β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; Pinteraction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.
- Subjects
LIPIDS; GENETIC polymorphism research; NUCLEAR magnetic resonance; PHYSICAL activity; WEIGHT loss; METFORMIN
- Publication
PLoS Genetics, 2012, Vol 8, Issue 8, p1
- ISSN
1553-7390
- Publication type
Article
- DOI
10.1371/journal.pgen.1002895