Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program. - PubMed - NCBI

Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program. - PubMed - NCBI

Circ Cardiovasc Genet. 2016 Oct 26. pii: CIRCGENETICS.116.001457. [Epub ahead of print]

Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program.

Varga TV1, Winters AH2, Jablonski KA3, Horton ES4, Khare-Ranade P5, Knowler WC6, Marcovina SM7, Renström F8, Watson KE9, Goldberg R10, Florez JC11, Pollin TI2, Franks PW12.

Author information

Abstract

BACKGROUND:

-We assessed whether 234 established dyslipidemia-associated loci modify the effects of metformin treatment and lifestyle intervention (vs. placebo control) on lipid and lipid sub-fraction levels in the Diabetes Prevention Program (DPP) randomized controlled trial.

METHODS AND RESULTS:

-We tested gene-treatment interactions in relation to baseline adjusted follow-up blood lipid concentrations (high and low density lipoprotein cholesterol [HDL-C, LDL-C], total cholesterol, triglycerides) and lipoprotein sub-fraction particle concentrations and size in 2,993 participants with pre-diabetes. Of the previously reported SNP associations, 32.5% replicated at P< 0.05 with baseline lipid traits. Trait-specific genetic risk scores (GRS) were robustly associated (3×10-4>P>1.1×10-16) with their respective baseline traits for all but two traits. Lifestyle modified the effect of the GRS for large HDL particle numbers, such that each risk allele of the GRSHDL-large was associated with lower concentrations of large HDL particles at follow-up in the lifestyle arm (β=-0.11 μmol/l per GRS risk allele; 95%CI -0.188, -0.033; P=5×10-3; Pinteraction=1×10-3 for lifestyle vs. placebo), but not in the metformin or placebo arms (P>0.05). In the lifestyle arm, participants with high genetic risk had more favorable or similar trait levels at 1-yr compared to participants at lower genetic risk at baseline for 17 of the 20 traits.

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-https://clinicaltrials.gov/; Unique Identifier: NCT00004992.

KEYWORDS:

genetic epidemiology; genetic polymorphism; genetics, human; genotype; intervention; lifestyle

PMID:

 

27784733

 

DOI:

 

10.1161/CIRCGENETICS.116.001457

[PubMed - as supplied by publisher]

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