Genetic Variation in FADS Genes and Plasma Cholesterol Levels in 2-Year-Old Infants: KOALA Birth Cohort Study

Carolina Moltó-Puigmartí,Carel Thijs,Dirkje S Postma,Monique Mommers,Marie Standl,Ronald P Mensink,Gerard H Koppelman,Joachim Heinrich,Eugène Jansen,John Penders,Jogchum Plat

doi:10.1371/journal.pone.0061671

Abstract

ObjectiveSingle nucleotide polymorphisms (SNPs) in genes involved in fatty acid metabolism (FADS1 FADS2 gene cluster) are associated with plasma lipid levels. We aimed to investigate whether these associations are already present early in life and compare the relative contribution of FADS SNPs vs traditional (non-genetic) factors as determinants of plasma lipid levels.MethodsInformation on infants’ plasma total cholesterol levels, genotypes of five FADS SNPs (rs174545, rs174546, rs174556, rs174561, and rs3834458), anthropometric data, maternal characteristics, and breastfeeding history was available for 521 2-year-old children from the KOALA Birth Cohort Study. For 295 of these 521 children, plasma HDLc and non-HDLc levels were also known. Multivariable linear regression analysis was used to study the associations of genetic and non-genetic determinants with cholesterol levels.ResultsAll FADS SNPs were significantly associated with total cholesterol levels. Heterozygous and homozygous for the minor allele children had about 4% and 8% lower total cholesterol levels than major allele homozygotes. In addition, homozygous for the minor allele children had about 7% lower HDLc levels. This difference reached significance for the SNPs rs174546 and rs3834458. The associations went in the same direction for non-HDLc, but statistical significance was not reached. The percentage of total variance of total cholesterol levels explained by FADS SNPs was relatively low (lower than 3%) but of the same order as that explained by gender and the non-genetic determinants together.Conclusions FADS SNPs are associated with plasma total cholesterol and HDLc levels in preschool children. This brings a new piece of evidence to explain how blood lipid levels may track from childhood to adulthood. Moreover, the finding that these SNPs explain a similar amount of variance in total cholesterol levels as the non-genetic determinants studied reveals the potential importance of investigating the effects of genetic variations in early life.

Highlights

Elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), and very-low-density lipoprotein cholesterol levels, and low levels of high-density lipoprotein cholesterol (HDLc) levels early in life play a role in the development of adult atherosclerosis, one of the major risk factors of coronary artery disease [1]
This may be partly explained by the fact that plasma lipid levels track from childhood into adulthood [2,3,4], and correlate with the extent of fatty streaks in early life [1,5]
In the study presented here we show that the associations between FADS single nucleotide polymorphisms (SNPs) genotypes and TC and HDLc levels are already present in 2-year-old preschool children

Summary

Introduction

Elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), and very-low-density lipoprotein cholesterol levels, and low levels of high-density lipoprotein cholesterol (HDLc) levels early in life play a role in the development of adult atherosclerosis, one of the major risk factors of coronary artery disease [1]. This may be partly explained by the fact that plasma lipid levels track from childhood into adulthood [2,3,4], and correlate with the extent of fatty streaks in early life (early atherosclerotic lesions which may progress to advanced atherosclerotic lesions and coronary artery disease) [1,5]. Many single nucleotide polymorphisms (SNPs), each with modest effects, have been found to explain part of the interindividual variability in plasma lipid levels [13,14,15,16]

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Conclusion