A1 Refereed original research article in a scientific journal

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




AuthorsAhola-Olli AV, Pitkänen N, Kettunen J, Oikonen MK, Mikkilä V, Lehtimäki T, Kähönen M, Pahkala K, Niinikoski H, Kangas AJ, Soininen P, Ala-Korpela M, Viikari JS, Rönnemaa T, Simell O, Raitakari OT

Publication year2014

JournalAmerican Journal of Clinical Nutrition

Journal name in sourceThe American journal of clinical nutrition

Journal acronymAm J Clin Nutr

Volume100

Issue6

First page 1569

Last page1577

Number of pages9

ISSN1938-3207

DOIhttps://doi.org/10.3945/ajcn.114.085027


Abstract

BACKGROUND\nElevated 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.\nOBJECTIVE\nWe aimed to identify genetic variants that modify the variation in serum lipid response to dietary fat quality.\nDESIGN\nWe 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.\nRESULTS\nIn 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.\nCONCLUSION\nThis 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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