Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: the Diabetes Prevention Program

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Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: the Diabetes Prevention Program

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Title: Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: the Diabetes Prevention Program
Author: Pollin, Toni I.; Isakova, Tamara; Jablonski, Kathleen A.; de Bakker, Paul I. W.; Taylor, Andrew; McAteer, Jarred; Pan, Qing; Horton, Edward S.; Delahanty, Linda M.; Altshuler, David; Shuldiner, Alan R.; Goldberg, Ronald B.; Florez, Jose Carlos; Franks, Paul W.

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Citation: Pollin, Toni I., Tamara Isakova, Kathleen A. Jablonski, Paul I. W. de Bakker, Andrew Taylor, Jarred McAteer, Qing Pan et al. 2012. Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: the diabetes prevention program. PLoS Genetics 8(8): e1002895.
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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=0.04–1×10\(^{−17}\)). Except for total HDL particles (r=−0.03, P=0.26), all components of the lipid profile correlated with the GRS (partial |r|=0.07–0.17, P=5×10\(^{−5}\)–1×10\(^{−19}\)). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β=+0.87, SEE±0.22 mg/dl/allele, P=8×10−5, P\(_{interaction}\)=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=−0.03, SEE±0.22 mg/dl/allele, P=0.90; P\(_{interaction}\)=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, P\(_{interaction}\)=0.01) but not in the placebo (β=−0.002, SEE±0.008 ln nmol/L/allele, P=0.74) or metformin (β=+0.013, SEE±0.008 nmol/L/allele, P=0.12; P\(_{interaction}\) = 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.
Published Version: doi:10.1371/journal.pgen.1002895
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431328/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10589802
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