The influence of six polymorphisms of uncoupling protein 3 (UCP3) gene and childhood obesity: a case-control study.

BACKGROUND: Obesity is defined as a multifactorial disease, marked by excessive accumulation of body fat, responsible for compromising the individual's health over the years. The energy balance is essential for the proper functioning of the body, as the individual needs to earn and spend energy in a compensatory way. Mitochondrial Uncoupling Proteins (UCP) help in energy expenditure through heat release and genetic polymorphisms could be responsible for reducing energy consumption to release heat and consequently generate an excessive accumulation of fat in the body. Thus, this study aimed to investigate the potential association between six UCP3 polymorphisms, that have not yet been represented in ClinVar®, and pediatric obesity susceptibility. METHODS: A case-control study was conducted with 225 children from Central Brazil. The groups were subdivided into obese (123) and eutrophic (102) individuals. The polymorphisms rs15763, rs1685354, rs1800849, rs11235972, rs647126, and rs3781907 were determined by real-time Polymerase Chain Reaction (qPCR). RESULTS: Biochemical and anthropometric evaluation of obese group showed higher levels of triglycerides, insulin resistance, and LDL-C and low level of HDL-C. Insulin resistance, age, sex, HDL-C, fasting glucose, triglyceride levels, and parents' BMI explained up to 50% of body mass deposition in the studied population. Additionally, obese mothers contribute 2 × more to the Z-BMI of their children than the fathers. The SNP rs647126 contributed to 20% to the risk of obesity in children and the SNP rs3781907 contribute to 10%. Mutant alleles of UCP3 increase the risk for triglycerides, total cholesterol, and HDL-C levels. The polymorphism rs3781907 is the only one that could not be a biomarker for obesity as the risk allele seem to be protective gains the increase in Z-BMI in our pediatric population. Haplotype analysis demonstrated two SNP blocks (rs15763, rs647126, and rs1685534) and (rs11235972 and rs1800849) that showed linkage disequilibrium, with LOD 76.3% and D' = 0.96 and LOD 57.4% and D' = 0.97, respectively. CONCLUSIONS: The causality between UCP3 polymorphism and obesity were not detected. On the other hand, the studied polymorphism contributes to Z-BMI, HOMA-IR, triglycerides, total cholesterol, and HDL-C levels. Haplotypes are concordant with the obese phenotype and contribute minimally to the risk of obesity.

Applicability of gene expression profile of childhood acute lymphoblastic leukemia at diagnosis and at the end of the induction phase of chemotherapy at a cancer hospital in the state of Goiás (Brazil).

The present study compared the gene expression pattern of some previously described genes at the time of diagnosis and after induction chemotherapy for childhood acute lymphoblastic leukemia (ALL) in patients submitted to Brazilian Childhood Leukemia Treatment Group (GBTLI) ALL-99 Protocol. Samples were obtained at the time of diagnosis from 16 patients with ALL and on the 28th day of induction chemotherapy the bone marrow samples were obtained from 12 children. The genes expression profiles in diagnostic and induction samples were analyzed by array-based qPCR and then related to the clinical and biological prognostic factors. The results showed significant associations (p ≤ 0.05) between gender and immunophenotype, immunophenotype and age, immunophenotype and risk group, presence of CD10 and RUNX1 expression, risk group, and immunophenotype. A significant positive correlation was observed between the expression levels of BAX and BCL2. There was a significant difference (p = 0.008) between the gene expression pattern at the time of diagnosis and after induction chemotherapy. The expression pattern of these genes after the induction phase of treatment approached the expression profile of the control group, indicating a good induction response in children treated according to the GBTLI ALL-99 protocol. The findings of the current research could be routinely useful for clinical practice and could assist in the discovery phase of medical applications.