Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program.
| Autor: | Varga TV; Dept of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund Univ, Malmö, Sweden., Winters AH; Division of Endocrinology, Diabetes & Nutrition, Dept of Medicine & Program in Genetics & Genomic Medicine, Univ of Maryland School of Medicine, Baltimore., Jablonski KA; The Biostatistics Center, George Washington Univ, Rockville, MD., Horton ES; Dept of Medicine, Harvard Medical School.; Joslin Diabetes Center, Boston, MA., Khare-Ranade P; Washington Univ, St. Louis, MO., Knowler WC; Diabetes Epidemiology & Clinical Research Section, NIDDK, Phoenix, AZ., Marcovina SM; Northwest Lipid Metabolism & Diabetes Research Laboratories, Univ of Washington, Seattle, WA., Renström F; Dept of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund Univ, Malmö, Sweden.; Dept of Biobank Research, Umeå Univ, Umeå, Sweden., Watson KE; Dept of Medicine, UCLA School of Medicine, CA., Goldberg R; Lipid Disorders Clinic, Division of Endocrinology, Diabetes & Metabolism, Leonard M. Miller School of Medicine, Univ of Miami, Miami, FL.; The Diabetes Research Institute, Leonard M. Miller School of Medicine, Univ of Miami, Miami, FL., Florez JC; Dept of Medicine, Harvard Medical School.; Program in Medical & Population Genetics, Broad Institute of Harvard & MIT, Cambridge.; Center for Human Genetic Research, Diabetes Unit, MGH.; Diabetes Research Center, Diabetes Unit, MGH., Pollin TI; Division of Endocrinology, Diabetes & Nutrition, Dept of Medicine & Program in Genetics & Genomic Medicine, Univ of Maryland School of Medicine, Baltimore., Franks PW; Dept of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund Univ, Malmö, Sweden.; Dept of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.; Dept of Public Health & Clinical Medicine, Umeå Univ, Umeå, Sweden. |
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| Jazyk: | angličtina |
| Zdroj: | Circulation. Cardiovascular genetics [Circ Cardiovasc Genet] 2016 Dec; Vol. 9 (6), pp. 495-503. Date of Electronic Publication: 2016 Oct 26. |
| DOI: | 10.1161/CIRCGENETICS.116.001457 |
| Abstrakt: | Background: We assessed whether 234 established dyslipidemia-associated loci modify the effects of metformin treatment and lifestyle intervention (versus placebo control) on lipid and lipid subfraction levels in the Diabetes Prevention Program randomized controlled trial. Methods and Results: We tested gene treatment interactions in relation to baseline-adjusted follow-up blood lipid concentrations (high-density lipoprotein [HDL] and low-density lipoprotein-cholesterol, total cholesterol, and triglycerides) and lipoprotein subfraction particle concentrations and size in 2993 participants with pre-diabetes. Of the previously reported single-nucleotide polymorphism associations, 32.5% replicated at P<0.05 with baseline lipid traits. Trait-specific genetic risk scores were robustly associated (3×10 -4 >P>1.1×10 -16 ) with their respective baseline traits for all but 2 traits. Lifestyle modified the effect of the genetic risk score for large HDL particle numbers, such that each risk allele of the genetic risk scores was associated with lower concentrations of large HDL particles at follow-up in the lifestyle arm (β=-0.11 µmol/L per genetic risk scores risk allele; 95% confidence interval, -0.188 to -0.033; P=5×10 -3 ; P Conclusions: Improvements in large HDL particle concentrations conferred by lifestyle may be diminished by genetic factors. Lifestyle intervention, however, was successful in offsetting unfavorable genetic loading for most lipid traits. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT00004992. (© 2016 American Heart Association, Inc.) |
| Databáze: | MEDLINE |
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