Interactions between genetic variants and dietary lipid composition: effects on circulating LDL cholesterol in children

Am J Clin Nutr. 2014 Dec;100(6):1569-77. doi: 10.3945/ajcn.114.085027. Epub 2014 Oct 8.


Background: Elevated serum low-density lipoprotein (LDL) cholesterol is a predictor of cardiovascular disease events, and the quality of dietary fat is known to influence serum concentrations of LDL cholesterol in children. Interindividual differences in response to diet exist, but the underlying genetic factors remain largely unknown.

Objective: We aimed to identify genetic variants that modify the variation in serum lipid response to dietary fat quality.

Design: We used data from 2 longitudinal Finnish cohorts designed to study risk factors for cardiovascular diseases. Large-scale genotyping was performed with Metabochip in a long-term randomized controlled dietary intervention trial, the Special Turku Coronary Risk Factor Intervention Project (STRIP), for discovery of genetic polymorphisms. The observational Cardiovascular Risk in Young Finns Study (YFS) with genome-wide genetic data was used as a replication sample for the initial findings. Dietary records were used to calculate the ratio of unsaturated to saturated fats. Interaction models and multiple follow-ups were used in the analysis.

Results: In the STRIP cohort, a variant within the PARK2 locus, rs9364628, showed moderate interaction with dietary fat quality and a consistent direction of effect in both scans on serum LDL-cholesterol concentration in children aged 5 and 7 y (P < 0.0084 and P < 0.0057, respectively). In the YFS cohort, we were unable to replicate the initial discovery signal, but rs12207186 within the PARK2 locus and dietary lipid quality had a stronger interaction effect on serum LDL-cholesterol concentration (P < 9.44 × 10(-5)) than did rs9364628 in children aged 6 y.

Conclusion: This genotyping study involving 2 cohorts of healthy Finnish children indicates a possible interaction between PARK2 variants and dietary fat quality on serum LDL-cholesterol concentration. This trial was registered at as NCT00223600.

Keywords: LDL cholesterol; PARK2; genetic; interaction; metabolomics.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics
  • Child
  • Child, Preschool
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood*
  • Dietary Fats / administration & dosage
  • Dietary Fats / analysis*
  • Fatty Acids / administration & dosage
  • Fatty Acids, Unsaturated / administration & dosage
  • Female
  • Finland / epidemiology
  • Follow-Up Studies
  • Genotyping Techniques
  • Humans
  • Longitudinal Studies
  • Male
  • Mental Recall
  • Metabolomics
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Triglycerides / blood
  • Ubiquitin-Protein Ligases / genetics*


  • Cholesterol, HDL
  • Cholesterol, LDL
  • Dietary Fats
  • Fatty Acids
  • Fatty Acids, Unsaturated
  • Triglycerides
  • Ubiquitin-Protein Ligases
  • parkin protein

Associated data