Does polymorphisms in PPAR and APOE genes modify associations between FADS, n-3 long-chain polyunsaturated fatty acids, and cardiometabolic markers in 8-11 year-old Danish children?

n-3 long-chain polyunsaturated fatty acids (LCPUFA) can improve cardiometabolic blood markers but studies in children are limited. Single nucleotide polymorphisms (SNPs) in the FADS genes, which encode fatty acid desaturases, influence endogenous LCPUFA production. Moreover, SNPs in genes that encode peroxisome proliferator-activated receptors (PPAR) and apolipoprotein E (apoE) may modulate the effects of n-3 LCPUFA. We explored whether FADS polymorphisms were associated with blood cholesterol and triacylglycerol, insulin and glucose and whether polymorphisms in PPARs and APOE modified associations between FADS or n-3 LCPUFA status and the cardiometabolic blood markers. We measured fasting cholesterol and triacylglycerol, insulin, glucose and n-3 LCPUFA in 757 Danish 8-11-year-old children and genotyped SNPs in FADS (rs1535 and rs174448), PPARG2 (rs1801282), PPARA (rs1800206) and APOE (rs7412+rs429358). Carriage of two FADS rs174448 major alleles was associated with lower triacylglycerol (P=0.027) and higher HDL cholesterol (P=0.047). Blood n-3 LCPUFA was inversely associated with triacylglycerol and insulin in PPARG2 minor allele carriers and positively with LDL cholesterol in major allele homozygotes (Pn-3LCPUFA×rs180182 0.11), but interaction between FADS rs1535 and APOE showed that rs1535 major allele homozygotes who also carried APOE2 had higher HDL cholesterol than all other genotype combinations (Prs1535×APOE =0.019, pairwise-P<0.05). This indicates that FADS genotypes, which increase endogenous LCPUFA production, may beneficially affect children's cardiometabolic profile in a partly APOE-dependent manner. Also, the degree to which children benefit from higher n-3 LCPUFA intake may depend on their PPARG2 genotype.