Identification of Novel Environmental Substances Relevant to Pediatric Graves' Disease.

Qin Xia,Kefeng Gu,Hui Sun,Xiuli Chen,Dandan Zhang,Wei Gu,Xu Xu,Linqi Chen,Rongrong Xie,Ting Chen,Fengyun Wang,Jingjing Liu,Haiying Wu

doi:10.3389/fendo.2021.691326

Abstract

Graves’ disease (GD) is the most common cause of hyperthyroidism, yet a relatively rare disease in the pediatric population. GD is a complex disorder influenced by both genetic and environmental factors. In this study, we aimed to find new environmental factors influencing the pathogenesis of GD. We investigated serum substances in 30 newly diagnosed GD children and 30 age- and gender-matched healthy controls. We measured total iodine by inductively coupled plasma-mass spectrometry (ICP-MS), analyzed perfluorinated compounds via ultra-high-performance liquid chromatography coupled with multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS), and explored other environmental substances using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–QTOF/MS) analysis. Twenty-nine single-nucleotide polymorphisms (SNPs) in eight genes related to GD were analyzed by SNaPshot. The serum total iodine was significantly higher in GD group, but its association with GD onset was weak, only with Exp(B) value near 1. The perfluorinated compound levels were not different between the two groups. More importantly, we found 16 environmental substances significantly different between GD and control groups, among which ponasterone A is a risk factor (p = 0.007 and Exp(B) = 14.14), while confertifoline is a protective factor against GD onset (p = 0.002 and Exp(B) = 0.001). We also identified 10 substances correlated significantly with thyroid indices in GD patients, among which seven associated with levels of the thyroid autoantibody TPOAb. No known SNPs were found predisposing GD. In this study, we explored a broad variety of environmental substances and identified novel factors that are potentially involved in the pediatric GD pathogenesis.

Highlights

Relatively rare in childhood, Graves’ disease (GD) is the most common cause of hyperthyroidism in the pediatric population [1, 2]
Previous epidemiological researches on GD environmental factors have studied the impact of iodine, infectious diseases, psychological stress, smoking, vitamin D, selenium, and immune modulating agents on GD pathogenesis [5], among which inappropriate iodine supply plays a major role in eliciting the occurrence of GD in genetically predisposed individuals [6]
We explored the serum levels of perfluorinated compounds via ultra-high-performance liquid chromatography coupled with multiple reaction monitoring mass spectrometry (UHPLC-MRM-mass spectroscopy (MS))

Summary

Introduction

Relatively rare in childhood, Graves’ disease (GD) is the most common cause of hyperthyroidism in the pediatric population [1, 2]. GD is a complex disease caused by a complex interplay among genetic and non-genetic factors, leading to sustained autoimmune response and loss of immune tolerance to thyroid antigens [5]. Studies on TDCs have implied their roles in the pathogenesis of autoimmune thyroid disease (AITD) [8]. Perfluorinated compounds are a group of recently reported TDCs proved to affect thyroid function in children [9, 10]. Their relationship with GD has not yet been explored

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Conclusion