The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Higher Body Mass Index and Fasting Glucose Levels: A Systematic Review and Meta-Analysis.

Xichang Wang,Weiping Teng,Haoyu Wang,Zhongyan Shan,Chuyuan Wang,Chenyu Zhang,Yaxin Lai,Kan Chen,Jiashu Li,Ali Abbara

doi:10.1155/2021/9914009

Abstract

Background Type 2 deiodinase (Dio2) is a selenoenzyme that is mainly expressed in the endoplasmic reticulum of the central nervous system, brown adipose tissue, and placenta and is responsible for outer ring deiodination of thyroxine (T4) to form biologically active triiodothyronine (T3). The Thr92Ala polymorphism of Dio2 has been found to be a potential risk factor for various diseases beyond the hypothalamus-pituitary-thyroid (HPT) axis. Methods We searched the relevant studies in the PubMed, Embase, and Cochrane Library databases and Google Scholar. A systematic review and meta-analysis of studies on the Thr92Ala polymorphism and metabolic parameters beyond the HPT axis (e.g., BMI, fasting glycemic traits, plasma lipid levels, and hypertension risk) were performed. Results Six eligible studies that analyzed the relationship between the Thr92Ala polymorphism and metabolic parameters beyond the thyroid were identified. All selected studies excluded patients with thyroid dysfunction, and diabetic patients were also excluded when fasting glucose and fasting insulin levels were meta-analyzed. The Thr92Ala polymorphism was found to be a significant risk factor for higher BMI (Std. mean difference 0.31 (0.01, 0.60), p = 0.04) and higher fasting glucose levels (Std. mean difference 1.18 (0.05, 2.31), p = 0.04). However, fasting insulin levels, plasma lipid levels, and hypertension risk showed a nonsignificant association with the Thr92Ala polymorphism. Conclusion Compared with euthyroid noncarriers (Thr/Thr), euthyroid Ala92-Dio2 carriers showed increased BMI levels, and Ala92-Dio2 carriers also had higher fasting plasma glucose levels than matched euthyroid nondiabetic noncarriers.

Highlights

Thyroid hormones are indispensable for maintaining the normal physiological function of various systems during the lifetime [1] and mainly consist of thyroxine (T4) and triiodothyronine (T3)
We assessed these articles in more detail by careful full-text examination, and six articles were included [13, 19,20,21,22,23], of which van der Deure et al analyzed the impact of Thr92Ala polymorphism on hypertension risk in two separate populations [23]
Kang et al compared the differences in fasting glucose and fasting insulin levels between different genotypes, we did not include the above data because diabetes patients were not excluded

Summary

Introduction

Thyroid hormones are indispensable for maintaining the normal physiological function of various systems during the lifetime [1] and mainly consist of thyroxine (T4) and triiodothyronine (T3). Type 2 deiodinase (Dio2) is a selenoenzyme that is mainly expressed in the endoplasmic reticulum of the central nervous system, brown adipose tissue, and placenta and is responsible for outer ring deiodination of thyroxine (T4) to form biologically active triiodothyronine (T3). A systematic review and meta-analysis of studies on the Thr92Ala polymorphism and metabolic parameters beyond the HPT axis (e.g., BMI, fasting glycemic traits, plasma lipid levels, and hypertension risk) were performed. The Thr92Ala polymorphism was found to be a significant risk factor for higher BMI (Std. mean difference 0.31 (0.01, 0.60), p = 0:04) and higher fasting glucose levels (Std. mean difference 1.18 (0.05, 2.31), p = 0:04). Fasting insulin levels, plasma lipid levels, and hypertension risk showed a nonsignificant association with the Thr92Ala polymorphism. Compared with euthyroid noncarriers (Thr/Thr), euthyroid Ala92-Dio carriers showed increased BMI levels, and Ala92-Dio carriers had higher fasting plasma glucose levels than matched euthyroid nondiabetic noncarriers

Objectives

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Conclusion