IGF2, LEPR, POMC, PPARG, and PPARGC1 gene variants are associated with obesity-related risk phenotypes in Brazilian children and adolescents

Abstract

Association studies of genetic variants and obesity and/or obesity-related risk factors have yielded contradictory results. The aim of the present study was to determine the possible association of five single-nucleotide polymorphisms (SNPs) located in the IGF2, LEPR, POMC, PPARG, and PPARGC1genes with obesity or obesity-related risk phenotypes. This case-control study assessed overweight (n=192) and normal-weight (n=211) children and adolescents. The SNPs were analyzed using minisequencing assays, and variables and genotype distributions between the groups were compared using one-way analysis of variance and Pearson's chi-square or Fisher's exact tests. Logistic regression analysis adjusted for age and gender was used to calculate the odds ratios (ORs) for selected phenotype risks in each group. No difference in SNP distribution was observed between groups. In children, POMC rs28932472(C) was associated with lower diastolic blood pressure (P=0.001), higher low-density lipoprotein (LDL) cholesterol (P=0.014), and higher risk in overweight children of altered total cholesterol (OR=7.35, P=0.006). In adolescents, IGF2 rs680(A) was associated with higher glucose (P=0.012) and higher risk in overweight adolescents for altered insulin (OR=10.08, P=0.005) and homeostasis model of insulin resistance (HOMA-IR) (OR=6.34, P=0.010). PPARG rs1801282(G) conferred a higher risk of altered insulin (OR=12.31, P=0.003), and HOMA-IR (OR=7.47, P=0.005) in overweight adolescents. PARGC1 rs8192678(A) was associated with higher triacylglycerols (P=0.005), and LEPR rs1137101(A) was marginally associated with higher LDL cholesterol (P=0.017). LEPR rs1137101(A) conferred higher risk for altered insulin, and HOMA-IR in overweight adolescents. The associations observed in this population suggested increased risk for cardiovascular diseases and/or type 2 diabetes later in life for individuals carrying these alleles.

Insulin-Like Growth Factors and Metabolic Syndrome in Obese Children

“…IGF2 polymorphisms have been associated with insulin sensitivity [16] and in Brazilian overweight adolescents, IGF2 variants have been related to a higher risk of insulin resistance [12]. Interestingly, we found that IGF-II was directly related to QUICKI index and inversely to HOMA, indicating a positive relationship with insulin sensitivity.…”

“…IGF2 polymorphisms were related to body weight, insulin sensitivity, fat-free mass, lipid profile, and blood pressure in humans [11]. In overweight adolescents, specific IGF2 variants have been related to higher risk of altered insulin and HOMA-IR [12] but its role in glucose metabolism is not clear and, to our knowledge, the association between IGF-II and MetS has not yet been investigated.…”

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“…ANOVA showed influence of Gln allele of rs1137101 polymorphism of LEPR gene (Table 3) Listed changes are traditionally linked with obesity in patients with DM2 [8,9] and presented in the table 3 according to decrease of influence degree of alleles of rs1137101 polymorphism of LEPR gene: increase of BMI > hyperleptinemia > dyslipidemia (increase of triglycerides and decrease of protective HDL), which were on the background of increase of insulin resistance.…”

Use of short-term high energy dietary for estimating transcriptional profiling of liver tissues in sheep

“…Interestingly, PGC-1a knock-out mice display impaired fatty acid oxidation, tricarboxylic acid (TCA) cycle metabolism, and liver gluconeogenesis [30]. On the other hand, Queiroz et al [31] observed an association between PGC-1a rs8192678 and higher triacylglycerol and glucose concentration in adolescents, which is similar to the results of an adult study [32]. Similarly, the expression levels of PGC-1a had been significantly down-regulated in our study.…”