Genetic Variation in FADS Genes and Plasma Cholesterol Levels in 2-Year-Old Infants

Single 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. Information 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. All 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. 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.