👤 Carmen Garcés

The DLK1 human gene encodes for the transmembrane EGF-like repeat-containing protein DLK1, which acts as a modulator of adipogenesis. A role for DLK1 in energy metabolism and lipid homeostasis has been suggested and DLK1 gene variants have been related to pubertal development. The aim of this study was to uncover DLK1 SNPs in a cohort of children and analyze their relationship with anthropometric and biochemical variables. Our population-based sample comprises 1237 healthy 6-to-8-year-old Caucasian children. The presence of five DLK1 SNPs (rs1802710, rs876374, rs7155375, rs57098752, and rs7149242) was analyzed by Real-Time PCR, using predesigned TaqMan™ Genotyping Assays. We observed that the SNPs rs1802710 and rs876374 were associated with BMI, and the prevalence of these two SNPs was different in normal-weight children compared to children with obesity. Related to biochemical variables, we found a significant association of the SNPs rs1802710, rs876374, and rs57098752 and their combination with Apo-B plasma concentrations after adjusting by BMI and sex. The SNPs rs1802710 and rs57098752 were also significantly associated with plasma levels of LDL-C and HDL-C, respectively. Our study reveals that DLK1 gene variants may influence both body weight and lipid homeostasis, affecting particularly to the Apo-B biology, in children. DLK1 polymorphisms are associated with BMI and with lipid levels, independently of BMI, early in life. Our data add to the existing literature the evidence that DLK1 gene variants impact on lipid metabolism. The confirmation at the population level that DLK1 genetic variants are associated with anthropometric and lipid variables sustains the role of DLK1 in obesity and related disorders and should lead to further studies aimed at clarifying this effect. Show less

Apolipoprotein A-V plays an important role in lipid metabolism regulation, particularly modulating triglyceride levels, as has been shown by many association studies in adults. The aim of this study was to analyse the effect of APOA5 on lipid profiles and fat-soluble vitamins (due to its strong relationship with triglyceride metabolism) in children. We determined polymorphisms -1131T>C and S19W in the APOA5 gene in 964 6-8-year-old participants of the 4P study and analysed the influence of the APOA5 gene on plasma lipid levels (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides), apolipolipoproteins (apo A-I and apo B) and fat-soluble antioxidant vitamin (α-tocopherol, γ-tocopherol, lycopene, α-carotene, β-carotene and retinol) levels. The allele frequencies of both polymorphisms were comparable to those described in adult Caucasian populations (0.08 and 0.07 for -1131T>C and S19W, respectively). Boys carrying the -1131C allele have a 12% increase in circulating triglyceride levels (p=0.016) and a 7% decrease in HDL phospholipid levels (p=0.016). Linked to its effect on triglycerides, boys with the -1131C allele also have a 5% increase in plasma α-tocopherol levels (p=0.032). This effect was not observed in female participants. Boys carrying the rare allele for the S19W polymorphism have a 4% increase in circulating cholesterol levels (p=0.045), whereas girls have a 9% increase in circulating triglyceride levels (p=0.029). Linked to its effect on triglycerides, female carriers of the rare allele for S19W also have a 6% increase in α-tocopherol levels (p=0.009). In children, the effect of APOA5 gene variants on triglyceride levels is related to gender, and because of the strong relationship between lipid metabolism and fat-soluble antioxidant vitamins, it also involves a significant elevation in α-tocopherol concentrations. Show less