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Plos Genetics : Genetic Modulation of Lipid Profiles Following Lifestyle Modification or Metformin Treatment ; the Diabetes Prevention Program, Volume 8

By Allison, David B.

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Book Id: WPLBN0003941782
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos Genetics : Genetic Modulation of Lipid Profiles Following Lifestyle Modification or Metformin Treatment ; the Diabetes Prevention Program, Volume 8  
Author: Allison, David B.
Volume: Volume 8
Language: English
Subject: Journals, Science, Genetics
Collections: Periodicals: Journal and Magazine Collection (Contemporary), PLoS Genetics
Historic
Publication Date:
Publisher: Plos

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Allison, D. B. (n.d.). Plos Genetics : Genetic Modulation of Lipid Profiles Following Lifestyle Modification or Metformin Treatment ; the Diabetes Prevention Program, Volume 8. Retrieved from http://www.ebooklibrary.org/


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Description : 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 = 0.04–1610217). 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=561025–1610219). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (b = +0.87, SEE60.22 mg/dl/allele, P=861025, Pinteraction = 0.02) in the lifestyle intervention group, but not in the placebo (b = +0.20, SEE60.22 mg/dl/allele, P = 0.35) or metformin (b =20.03, SEE60.22 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 (b = +0.30, SEE60.012 ln nmol/L/ allele, P = 0.01, Pinteraction = 0.01) but not in the placebo (b =20.002, SEE60.008 ln nmol/L/allele, P = 0.74) or metformin (b = +0.013, SEE60.008 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.


 

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