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Interactions between genetic variants and dietary lipid composition: effects on circulating LDL cholesterol in
Ari V Ahola-Olli1, Niina Pitkänen1, Johannes Kettunen1
1From the Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland (AVA-O, NP, MKO, VM, KP, and TR); the Department of Food and Environmental Sciences (VM) and the Institute for Molecular Medicine Finland (FIMM) (JK), University of Helsinki, Helsinki, Finland; the Department of Clinical Chemistry, Fimlab Laboratories, Pirkanmaa Hospital District, School of Medicine, University of Tampere, Tampere, Finland (TL); the Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland (MK); Paavo Nurmi Centre, Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku, Turku, Finland (KP); the Department of Pediatrics, Turku University Hospital, Turku, Finland (HN and OS); Computational Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland (AJK, PS, and MA-K); NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland (PS and MA-K); Oulu University Hospital, Oulu, Finland (MA-K); Computational Medicine, School of Social and Community Medicine and the Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom (MA-K); the Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland (JSV and TR); and the Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland (OTR).
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 clinicaltrials.gov as NCT00223600.
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