Association of Type 2 Deiodinase Thr92Ala Polymorphism with Pediatric Obesity in Japanese Children: A Case-Control Study

Overview

Journal Children (Basel)

Specialty Health Services

Date 2022 Oct 27

PMID 36291357

Authors

Takeshi Ota

Jun Mori

Yasuhiro Kawabe

Hidechika Morimoto

Shota Fukuhara

Kazuki Kodo

Satoru Sugimoto

Kitaro Kosaka

Hisakazu Nakajima

Hajime Hosoi

Affiliations

Soon will be listed here.

Abstract

Genetic factors play critical roles in the onset and progression of obesity. Brown adipose tissue (BAT) activity is also critical for adiposity. The objective of this study was to evaluate the prevalence and effects of BAT gene polymorphisms in pediatric obesity. This case-control study included 270 non-obese and 86 obese children. All participants underwent genotyping for type 2 deiodinase (DIO2) Thr92Ala (rs225014). The prevalence of the homozygous Ala/Ala allele of the DIO2 gene in the obese group was 15.1% versus 6.3% in the non-obese group, resulting in an odds ratio (OR) of 3.393 ( = 0.003). The results of this study indicate that the homozygous Ala/Ala allele of the DIO2 gene is associated with an increased risk of pediatric obesity and suggest that pediatric obesity might be suitable for assessing the association with gene polymorphisms related to BAT, especially DIO2 Thr92Ala.

References

Luongo C, Dentice M, Salvatore D . Deiodinases and their intricate role in thyroid hormone homeostasis. Nat Rev Endocrinol. 2019; 15(8):479-488. DOI: 10.1038/s41574-019-0218-2. View

Maes H, Neale M, Eaves L . Genetic and environmental factors in relative body weight and human adiposity. Behav Genet. 1997; 27(4):325-51. DOI: 10.1023/a:1025635913927. View

Kawabe Y, Mori J, Morimoto H, Yamaguchi M, Miyagaki S, Ota T . ACE2 exerts anti-obesity effect via stimulating brown adipose tissue and induction of browning in white adipose tissue. Am J Physiol Endocrinol Metab. 2019; 317(6):E1140-E1149. DOI: 10.1152/ajpendo.00311.2019. View

Dobashi K . Evaluation of Obesity in School-Age Children. J Atheroscler Thromb. 2015; 23(1):32-8. DOI: 10.5551/jat.29397. View

Hauerslev M, Narang T, Gray N, Samuels T, Bhutta Z . Childhood obesity on the rise during COVID-19: A request for global leaders to change the trajectory. Obesity (Silver Spring). 2021; 30(2):288-291. PMC: 8662111. DOI: 10.1002/oby.23307. View

Maia A, Kim B, Huang S, Harney J, Larsen P . Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. J Clin Invest. 2005; 115(9):2524-33. PMC: 1190373. DOI: 10.1172/JCI25083. View

Chen Y, Wang X, Shen Z, Fan P, Liu R, Liu Y . Effect of the beta-3 adrenergic receptor Trp64Arg and uncoupling protein 1-3826 A>G genotypes on lipid and apolipoprotein levels in overweight/obese and non-obese Chinese subjects. Lipids Health Dis. 2015; 14:34. PMC: 4410578. DOI: 10.1186/s12944-015-0029-y. View

Kotani K, Sakane N, Saiga K, Adachi S, Shimohiro H, Mu H . Relationship between A-3826G polymorphism in the promoter of the uncoupling protein-1 gene and high-density lipoprotein cholesterol in Japanese individuals: a cross-sectional study. Arch Med Res. 2007; 39(1):142-6. DOI: 10.1016/j.arcmed.2007.07.002. View

Enerback S . Human brown adipose tissue. Cell Metab. 2010; 11(4):248-52. DOI: 10.1016/j.cmet.2010.03.008. View

10.

Mullur R, Liu Y, Brent G . Thyroid hormone regulation of metabolism. Physiol Rev. 2014; 94(2):355-82. PMC: 4044302. DOI: 10.1152/physrev.00030.2013. View

11.

Morimoto H, Mori J, Nakajima H, Kawabe Y, Tsuma Y, Fukuhara S . Angiotensin 1-7 stimulates brown adipose tissue and reduces diet-induced obesity. Am J Physiol Endocrinol Metab. 2017; 314(2):E131-E138. DOI: 10.1152/ajpendo.00192.2017. View

12.

Cantara S, Ricci C, Maino F, Marzocchi C, Pacini F, Castagna M . Variants in MCT10 protein do not affect FT3 levels in athyreotic patients. Endocrine. 2019; 66(3):551-556. DOI: 10.1007/s12020-019-02001-z. View

13.

Mentuccia D, Proietti-Pannunzi L, Tanner K, Bacci V, Pollin T, Poehlman E . Association between a novel variant of the human type 2 deiodinase gene Thr92Ala and insulin resistance: evidence of interaction with the Trp64Arg variant of the beta-3-adrenergic receptor. Diabetes. 2002; 51(3):880-3. DOI: 10.2337/diabetes.51.3.880. View

14.

Tokgoz Y, Isik I, Akbari S, Kume T, Sayin O, Erdal E . Perilipin polymorphisms are risk factors for the development of obesity in adolescents? A case-control study. Lipids Health Dis. 2017; 16(1):52. PMC: 5343409. DOI: 10.1186/s12944-017-0440-7. View

15.

Ghosh S, Langefeld C, Ally D, Watanabe R, Hauser E, Magnuson V . The W64R variant of the beta3-adrenergic receptor is not associated with type II diabetes or obesity in a large Finnish sample. Diabetologia. 1999; 42(2):238-44. DOI: 10.1007/s001250051144. View

16.

Mentuccia D, Thomas M, Coppotelli G, Reinhart L, Mitchell B, Shuldiner A . The Thr92Ala deiodinase type 2 (DIO2) variant is not associated with type 2 diabetes or indices of insulin resistance in the old order of Amish. Thyroid. 2005; 15(11):1223-7. DOI: 10.1089/thy.2005.15.1223. View

17.

Isojima T, Yokoya S . The value of anthropometric indices for childhood obesity in Japan. Ann Hum Biol. 2019; 46(4):293-297. DOI: 10.1080/03014460.2019.1643404. View

18.

Cioffi F, Gentile A, Silvestri E, Goglia F, Lombardi A . Effect of Iodothyronines on Thermogenesis: Focus on Brown Adipose Tissue. Front Endocrinol (Lausanne). 2018; 9:254. PMC: 5974034. DOI: 10.3389/fendo.2018.00254. View

19.

Haslam D, James W . Obesity. Lancet. 2005; 366(9492):1197-209. DOI: 10.1016/S0140-6736(05)67483-1. View

20.

Gilsanz V, Chung S, Jackson H, Dorey F, Hu H . Functional brown adipose tissue is related to muscle volume in children and adolescents. J Pediatr. 2010; 158(5):722-6. PMC: 3319332. DOI: 10.1016/j.jpeds.2010.11.020. View