Does polymorphisms in PPAR and APOE genes modify associations between fatty acid desaturase (FADS), n-3 long-chain PUFA and cardiometabolic markers in 8–11-year-old Danish children?

Abstract

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<0.01). Associations between n-3 LCPUFA and cardiometabolic markers were not modified by APOE genotype (Pn-3LCPUFA×APOE>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.

Effects of PPARG and PPARGC1A gene polymorphisms on obesity markers

“…This is in agreement with the results of previous research, where fish oil reduced plasma glucose only in carriers of the rs1801282 G allele in the PPRG2 gene ( 74 ). Damsgaard et al ( 73 ) found an inverse association between seric n -3 LCPUFA and triglycerides only in the PPARG2 rs1801282 G allele carriers, which concurs with the results of a previous study in infants ( 74 ). Blood n -3 LCPUFA was positively associated with LDL-c in children who were C allele homozygous of the rs1801282 SNP in the PPARG2 gene ( 73 ).…”

“…A recent study found that PPRAG rs1801282 modified the association between n -3 long-chain PUFA (LCPUFA) and serum insulin with an inverse association in minor allele (Ala12 = G) carriers only and no interaction between fatty acid desaturase FADS or n -3 LCPUFA and plasma glucose ( 73 ). This is in agreement with the results of previous research, where fish oil reduced plasma glucose only in carriers of the rs1801282 G allele in the PPRG2 gene ( 74 ).…”

Metabolic Biomarkers in Adults with Type 2 Diabetes: The Role of PPAR-γ2 and PPAR-β/δ Polymorphisms

“…Lifestyle factors contribute to the high variation observed in glycemic responses among individuals as well as interactions between SNPs. Factors such as diet [54], weight loss [55], exercise [59], and fatty acid levels [60] have been documented to influence or interact with SNPs. Furthermore, gene-gene interactions should be taken into account when assessing the influence of SNPs in metabolic biomarkers.…”

The function of omega-3 polyunsaturated fatty acids in response to cadmium exposure

“…Current research shows, n-3 PUFAs control the expression of a great variety of genes through different transcriptional factors, such as SREBP ( 169 ), PPARs ( 170 ), ChREBP ( 171 ), and NF-κB ( 172 ), which mainly regulate target gene transcription that encodes proteins involved in lipid and carbohydrate metabolism, thermogenesis, and inflammatory processes. However, it is important to point out that further studies are needed to elucidate these roles and to better understand the beneficial role of n-3 PUFAs in the mechanism of Cd exposure-induced disease, and to probe into their function as protective nutrients, aiming to prevent or treat the development of Cd exposure-related diseases.…”