title: Genetic variation in FADS genes and plasma cholesterol levels in 2-year-old infants: KOALA Birth Cohort Study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  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.
authors.affiliation: Department of Epidemiology, CAPHRI School for Public Health and Primary Care, Maastricht University Medical Centre, Maastricht, The Netherlands. Carolina.molto@maastrichtuniversity.nl
authors.forename: Carolina
authors.initials: C
authors.lastname: Moltó-Puigmartí
authors.forename: Eugène
authors.initials: E
authors.lastname: Jansen
authors.forename: Joachim
authors.initials: J
authors.lastname: Heinrich
authors.forename: Marie
authors.initials: M
authors.lastname: Standl
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mensink
authors.forename: Jogchum
authors.initials: J
authors.lastname: Plat
authors.forename: John
authors.initials: J
authors.lastname: Penders
authors.forename: Monique
authors.initials: M
authors.lastname: Mommers
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Koppelman
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Carel
authors.initials: C
authors.lastname: Thijs
mesh_terms: D000886:Anthropometry; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood*; D015331:Cohort Studies; D000090943:Delta-5 Fatty Acid Desaturase; D044943:Fatty Acid Desaturases / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008075:Lipoproteins, HDL / Q000097:blood; D005810:Multigene Family / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D000090943:Delta-5 Fatty Acid Desaturase; D008075:Lipoproteins, HDL; D002784:Cholesterol; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human; C533241:FADS2 protein, human