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Genetic Modulation ...
Genetic Modulation of Lipid Profiles following Lifestyle Modification or Metformin Treatment: The Diabetes Prevention Program
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Pollin, Toni I. (författare)
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Isakova, Tamara (författare)
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Jablonski, Kathleen A. (författare)
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de Bakker, Paul I. W. (författare)
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Taylor, Andrew (författare)
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McAteer, Jarred (författare)
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Pan, Qing (författare)
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Horton, Edward S. (författare)
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Delahanty, Linda M. (författare)
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Altshuler, David (författare)
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Shuldiner, Alan R. (författare)
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Goldberg, Ronald B. (författare)
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Florez, Jose C. (författare)
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- Franks, Paul (författare)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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(creator_code:org_t)
- 2012-08-30
- 2012
- Engelska.
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 8:8
- Relaterad länk:
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https://portal.resea... (primary) (free)
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http://dx.doi.org/10... (free)
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https://journals.plo...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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- Av författaren/redakt...
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Pollin, Toni I.
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Isakova, Tamara
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Jablonski, Kathl ...
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de Bakker, Paul ...
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Taylor, Andrew
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McAteer, Jarred
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visa fler...
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Pan, Qing
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Horton, Edward S ...
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Delahanty, Linda ...
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Altshuler, David
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Shuldiner, Alan ...
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Goldberg, Ronald ...
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Florez, Jose C.
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Franks, Paul
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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PLoS Genetics
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Lunds universitet