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dc.contributor.authorPollin, Toni I.
dc.contributor.authorIsakova, Tamara
dc.contributor.authorJablonski, Kathleen A.
dc.contributor.authorde Bakker, Paul I. W.
dc.contributor.authorTaylor, Andrew
dc.contributor.authorMcAteer, Jarred
dc.contributor.authorPan, Qing
dc.contributor.authorHorton, Edward S.
dc.contributor.authorDelahanty, Linda M.
dc.contributor.authorAltshuler, David
dc.contributor.authorShuldiner, Alan R.
dc.contributor.authorGoldberg, Ronald B.
dc.contributor.authorFlorez, Jose Carlos
dc.contributor.authorFranks, Paul W.
dc.date.accessioned2013-04-26T18:29:35Z
dc.date.issued2012
dc.identifier.citationPollin, 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.en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10589802
dc.description.abstractWeight-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.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pgen.1002895en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431328/pdf/en_US
dash.licenseLAA
dc.subjectMedicineen_US
dc.subjectDrugs and Devicesen_US
dc.subjectPharmacogeneticsen_US
dc.subjectEndocrinologyen_US
dc.subjectDiabetic Endocrinologyen_US
dc.subjectDiabetes Mellitus Type 2en_US
dc.titleGenetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: the Diabetes Prevention Programen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Geneticsen_US
dash.depositing.authorHorton, Edward S.
dc.date.available2013-04-26T18:29:35Z
dc.identifier.doi10.1371/journal.pgen.1002895*
dash.authorsorderedfalse
dash.contributor.affiliatedHorton, Edward
dash.contributor.affiliatedDelahanty, Linda
dash.contributor.affiliatedFlorez, Jose
dash.contributor.affiliatedAltshuler, David


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