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]

Public Health Genomics Knowledge Base (v1.2)

DIABETES

Last Updated: Nov 02, 2016

• It's Your Life. Treat Your Diabetes Well. 
• Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program.
  Varga Tibor V, et al. Circulation. Cardiovascular genetics 2016 10
• Pancreatic cancer risks associated with prediagnostic plasma levels of leptin and leptin receptor genetic polymorphisms.
  Babic Ana, et al. Cancer research 2016 10
• Prospective functional classification of all possible missense variants in PPARG.
  Majithia Amit R, et al. Nature genetics 2016 10
• Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans.
  Mez Jesse, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association 2016 10
• The impact of access to health services on prediabetes awareness: A population-based study.
  Campbell Tonya J et al. Preventive medicine 2016 Sep 937-13
• Impact of Genetic Loci Identified in Genome-Wide Association Studies on Diabetic Retinopathy in Chinese Patients With Type 2 Diabetes.
  Cheung Chloe Y Y, et al. Investigative ophthalmology & visual science 2016 10 (13) 5518-5524
• Association of Rs2071410 on Furin with Transient Ischemic Attack Susceptibility and Prognosis in a Chinese Population.
  Sun Qin-Xiang, et al. Medical science monitor : international medical journal of experimental and clinical research 2016 10 3828-3834
• Differences in food intake and genetic variability in taste receptors between Czech pregnant women with and without gestational diabetes mellitus.
  Bartáková Vendula, et al. European journal of nutrition 2016 10
• Impact of the TCF7L2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia.
  Kristensen Peter Lommer, et al. Endocrine connections 2016 10
• Association between PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), GCKR (rs780094), and elevated transaminase levels in overweight/obese Mexican adults.
  Flores Yvonne N, et al. Molecular biology reports 2016 10
• Combined Deletion of Slc30a7 and Slc30a8 Unmasks a Critical Role for ZnT8 in Glucose-Stimulated Insulin Secretion.
  Syring Kristen E, et al. Endocrinology 2016 10 en20161573
• OS 05-01 PROX1 GENE CC GENOTYPE AS A MAJOR DETERMINANT OF EARLY ONSET OF T2D AND CARDIOVASCULAR COMPLICATIONS IN SLAVIC SUBJECTS FROM ADVANCE STUDY.
  Hamet Pavel, et al. Journal of hypertension 2016 9 e58
• YIA 03-01 VALIDATION OF GENETIC DETERMINANTS OF UNMET NEEDS IN THE TREATMENT OF KIDNEY DISEASE IN TYPE-2 DIABETES.
  Simon Paul, et al. Journal of hypertension 2016 9 e204
• Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.
  Cheung Chloe Y Y, et al. Diabetologia 2016 10

• CDC Information (15)
• CDC-Authored Pub (12)

• Human (64)
• Pathogen (8)

• Human (9399)
• Pathogen (0)

• Human (106)
• Pathogen (0)

• Guidelines (8)
• Tier Table (6)
• Synthesis (15)

• Huamn (21)
• Pathogen (0)

Relevant Resources

• Cancer Genomics and Epidemiology Navigator (CGEN)
• Genetics and Genomics Competencies Center (G2C2)
• NIH Genetic Testing Registry
• NIH MedGen Database
• Online Mendelian Inheritance in Man (OMIM)
• PharmGKB