Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: the Diabetes Prevention Program.
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...
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2012-01-01
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doaj-1511d67fc92e4fdfa24084c24f50a2682020-11-25T02:23:50ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-0188e100289510.1371/journal.pgen.1002895Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: the Diabetes Prevention Program.Toni I PollinTamara IsakovaKathleen A JablonskiPaul I W de BakkerAndrew TaylorJarred McAteerQing PanEdward S HortonLinda M DelahantyDavid AltshulerAlan R ShuldinerRonald B GoldbergJose C FlorezPaul W FranksDiabetes Prevention Program Research GroupWeight-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.http://europepmc.org/articles/PMC3431328?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Toni I Pollin Tamara Isakova Kathleen A Jablonski Paul I W de Bakker Andrew Taylor Jarred McAteer Qing Pan Edward S Horton Linda M Delahanty David Altshuler Alan R Shuldiner Ronald B Goldberg Jose C Florez Paul W Franks Diabetes Prevention Program Research Group |
spellingShingle |
Toni I Pollin Tamara Isakova Kathleen A Jablonski Paul I W de Bakker Andrew Taylor Jarred McAteer Qing Pan Edward S Horton Linda M Delahanty David Altshuler Alan R Shuldiner Ronald B Goldberg Jose C Florez Paul W Franks Diabetes Prevention Program Research Group Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: the Diabetes Prevention Program. PLoS Genetics |
author_facet |
Toni I Pollin Tamara Isakova Kathleen A Jablonski Paul I W de Bakker Andrew Taylor Jarred McAteer Qing Pan Edward S Horton Linda M Delahanty David Altshuler Alan R Shuldiner Ronald B Goldberg Jose C Florez Paul W Franks Diabetes Prevention Program Research Group |
author_sort |
Toni I Pollin |
title |
Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: the Diabetes Prevention Program. |
title_short |
Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: the Diabetes Prevention Program. |
title_full |
Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: the Diabetes Prevention Program. |
title_fullStr |
Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: the Diabetes Prevention Program. |
title_full_unstemmed |
Genetic modulation of lipid profiles following lifestyle modification or metformin treatment: the Diabetes Prevention Program. |
title_sort |
genetic modulation of lipid profiles following lifestyle modification or metformin treatment: the diabetes prevention program. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2012-01-01 |
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 = 0.04-1 × 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. |
url |
http://europepmc.org/articles/PMC3431328?pdf=render |
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