Skip to main content
Top
Published in: BMC Pediatrics 1/2023

Open Access 01-12-2023 | Obesity | Research

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

Authors: Jakeline S. Fortes, Renata M. Pinto, Raissa F. de Souza, Fernanda R. Godoy, Raphael S. da Cruz, Daniela de M e Silva, Hugo P. Leite Filho, Aparecido D. da Cruz, Lysa B. Minasi

Published in: BMC Pediatrics | Issue 1/2023

Login to get access

Abstract

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.
Literature
4.
go back to reference Wannmacher, L. Obesidade como fator de risco para morbidade e mortalidade: evidências sobre o manejo com medidas não medicamentosas. In: Uso Racional de Medicamentos: fundamentação em condutas terapêuticas e nos macroprocessos da Assistência Farmacêutica. Organização Pan-Americana da Saúde/Organização Mundial da Saúde (OPAS/OMS) no Brasil. 2016;1:7. https://www.paho.org/bra/dmdocuments/Fasciculo%207.pdf. Accessed 16 Jan 2021. Wannmacher, L. Obesidade como fator de risco para morbidade e mortalidade: evidências sobre o manejo com medidas não medicamentosas. In: Uso Racional de Medicamentos: fundamentação em condutas terapêuticas e nos macroprocessos da Assistência Farmacêutica. Organização Pan-Americana da Saúde/Organização Mundial da Saúde (OPAS/OMS) no Brasil. 2016;1:7. https://​www.​paho.​org/​bra/​dmdocuments/​Fasciculo%20​7.​pdf. Accessed 16 Jan 2021.
10.
go back to reference de Souza BM, Brondani LA, Boucas AP, Sortica DA, Kramer CK, Canani LH, ... & Crispim, D. et al. Associations between UCP1 -3826A/G, UCP2 -866G/A, Ala55Val and Ins/Del, and UCP3 -55C/T polymorphisms and susceptibility to type 2 diabetes mellitus: case-control study and meta-analysis. Plos One. 2013. https://doi.org/10.1371/journal.pone.0054259. de Souza BM, Brondani LA, Boucas AP, Sortica DA, Kramer CK, Canani LH, ... & Crispim, D. et al. Associations between UCP1 -3826A/G, UCP2 -866G/A, Ala55Val and Ins/Del, and UCP3 -55C/T polymorphisms and susceptibility to type 2 diabetes mellitus: case-control study and meta-analysis. Plos One. 2013. https://​doi.​org/​10.​1371/​journal.​pone.​0054259.
40.
45.
go back to reference Hamada T, Kotani K, Fujiwara S, Sano Y, Domichi M, Tsuzaki K, Sakane N. The common− 55 C/T polymorphism in the promoter region of the uncoupling protein 3 gene reduces prevalence of obesity and elevates serum high-density lipoprotein cholesterol levels in the general Japanese population. Metabolism-Clinical and Experimental. 2008. https://doi.org/10.1016/j.metabol.2007.10.019.CrossRefPubMed Hamada T, Kotani K, Fujiwara S, Sano Y, Domichi M, Tsuzaki K, Sakane N. The common− 55 C/T polymorphism in the promoter region of the uncoupling protein 3 gene reduces prevalence of obesity and elevates serum high-density lipoprotein cholesterol levels in the general Japanese population. Metabolism-Clinical and Experimental. 2008. https://​doi.​org/​10.​1016/​j.​metabol.​2007.​10.​019.CrossRefPubMed
48.
go back to reference Schnor NPP, Verlengia R, Novais PFS, Crisp AH, Leite CVDS, Rasera-Junior I, Oliveira MRMD. Association of 5-HT2C (rs3813929) and UCP3 (rs1800849) gene polymorphisms with type 2 diabetes in obese women candidates for bariatric surgery. Archives of endocrinology and metabolismo. 2017. https://doi.org/10.1590/2359-3997000000260.CrossRef Schnor NPP, Verlengia R, Novais PFS, Crisp AH, Leite CVDS, Rasera-Junior I, Oliveira MRMD. Association of 5-HT2C (rs3813929) and UCP3 (rs1800849) gene polymorphisms with type 2 diabetes in obese women candidates for bariatric surgery. Archives of endocrinology and metabolismo. 2017. https://​doi.​org/​10.​1590/​2359-3997000000260.CrossRef
50.
go back to reference Su, M., Chen, X., Chen, Y., Wang, C., Li, S., Ying, X., Fu, C. et al. UCP2 and UCP3 variants and gene-environment interaction associated with prediabetes and T2DM in a rural population: a case control study in China. BMC Medical Gen. https://doi.org/10.1186/s12881-018-0554-4. Su, M., Chen, X., Chen, Y., Wang, C., Li, S., Ying, X., Fu, C. et al. UCP2 and UCP3 variants and gene-environment interaction associated with prediabetes and T2DM in a rural population: a case control study in China. BMC Medical Gen. https://​doi.​org/​10.​1186/​s12881-018-0554-4.
Metadata
Title
The influence of six polymorphisms of uncoupling protein 3 (UCP3) gene and childhood obesity: a case–control study
Authors
Jakeline S. Fortes
Renata M. Pinto
Raissa F. de Souza
Fernanda R. Godoy
Raphael S. da Cruz
Daniela de M e Silva
Hugo P. Leite Filho
Aparecido D. da Cruz
Lysa B. Minasi
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2023
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-023-03905-6

Other articles of this Issue 1/2023

BMC Pediatrics 1/2023 Go to the issue