TY - JOUR
T1 - Genetic Variation in FADS Genes and Plasma Cholesterol Levels in 2-Year-Old Infants
T2 - KOALA Birth Cohort Study
AU - Molto-Puigmarti, Carolina
AU - Jansen, Eugene
AU - Heinrich, Joachim
AU - Standl, Marie
AU - Mensink, Ronald P.
AU - Plat, Jogchum
AU - Penders, John
AU - Mommers, Monique
AU - Koppelman, Gerard H.
AU - Postma, Dirkje S.
AU - Thijs, Carel
PY - 2013/5/8
Y1 - 2013/5/8
N2 - 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 nongenetic 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.
AB - 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 nongenetic 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.
KW - POLYUNSATURATED FATTY-ACIDS
KW - CORONARY-ARTERY-DISEASE
KW - PRESCHOOL-CHILDREN
KW - BLOOD CHOLESTEROL
KW - SERUM-CHOLESTEROL
KW - LIPOPROTEIN CONCENTRATIONS
KW - MULTIRACIAL SAMPLE
KW - LIPID-LEVELS
KW - ASSOCIATION
KW - VARIANTS
U2 - 10.1371/journal.pone.0061671
DO - 10.1371/journal.pone.0061671
M3 - Article
C2 - 23667444
SN - 1932-6203
VL - 8
JO - PLoS ONE
JF - PLoS ONE
IS - 5
M1 - e61671
ER -