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  • Pollin, Toni I. (author)

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

  • Article/chapterEnglish2012

Publisher, publication year, extent ...

  • 2012-08-30
  • Public Library of Science (PLoS),2012
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:e597808e-a518-4af1-bfe3-cc00a99a98a1
  • https://lup.lub.lu.se/record/3191519URI
  • https://doi.org/10.1371/journal.pgen.1002895DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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 = 0.04-1x10(-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=5x10(-5)-1x10(-19)). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (beta = +0.87, SEE +/- 0.22 mg/dl/allele, P=8x10(-5), P-interaction = 0.02) in the lifestyle intervention group, but not in the placebo (beta = +0.20, SEE +/- 0.22 mg/dl/allele, P = 0.35) or metformin (beta = -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 (beta = +0.30, SEE +/- 0.012 ln nmol/L/allele, P = 0.01, P-interaction = 0.01) but not in the placebo (beta = 20.002, SEE +/- 0.008 ln nmol/L/allele, P = 0.74) or metformin (beta = +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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Isakova, Tamara (author)
  • Jablonski, Kathleen A. (author)
  • de Bakker, Paul I. W. (author)
  • Taylor, Andrew (author)
  • McAteer, Jarred (author)
  • Pan, Qing (author)
  • Horton, Edward S. (author)
  • Delahanty, Linda M. (author)
  • Altshuler, David (author)
  • Shuldiner, Alan R. (author)
  • Goldberg, Ronald B. (author)
  • Florez, Jose C. (author)
  • Franks, PaulLund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-plf (author)
  • Genetisk och molekylär epidemiologiForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:PLoS Genetics: Public Library of Science (PLoS)8:81553-7404

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