Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?

Abstract. Background:. Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with child...

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Main Authors: Zichen Feng, Ning An, Fangfang Yu, Jun Ma, Na Li, Yuhui Du, Meng Guo, Kaihong Xu, Xiangbo Hou, Zhiyuan Li, Guoyu Zhou, Yue Ba, Jing Ni
Format: Article
Language:English
Published: Wolters Kluwer 2022-08-01
Series:Chinese Medical Journal
Online Access:http://journals.lww.com/10.1097/CM9.0000000000002062
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author Zichen Feng
Ning An
Fangfang Yu
Jun Ma
Na Li
Yuhui Du
Meng Guo
Kaihong Xu
Xiangbo Hou
Zhiyuan Li
Guoyu Zhou
Yue Ba
Jing Ni
author_facet Zichen Feng
Ning An
Fangfang Yu
Jun Ma
Na Li
Yuhui Du
Meng Guo
Kaihong Xu
Xiangbo Hou
Zhiyuan Li
Guoyu Zhou
Yue Ba
Jing Ni
author_sort Zichen Feng
collection DOAJ
description Abstract. Background:. Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored. Methods:. A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UFCr) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UFCr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence. Results:. In the high fluoride group, children's IQ scores decreased by 2.502 when the UFCr level increased by 1.0 mg/L (β = −2.502, 95% confidence interval [CI]:−4.411, −0.593), and the possibility for having “excellent” intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group (P < 0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05). Conclusion:. Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.
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spelling doaj.art-571a5563eff84a6ba75a915a75a63fb62022-12-22T02:43:37ZengWolters KluwerChinese Medical Journal0366-69992542-56412022-08-01135151846185410.1097/CM9.0000000000002062202208050-00011Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?Zichen FengNing AnFangfang YuJun MaNa LiYuhui DuMeng GuoKaihong XuXiangbo HouZhiyuan LiGuoyu ZhouYue BaJing NiAbstract. Background:. Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored. Methods:. A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UFCr) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UFCr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence. Results:. In the high fluoride group, children's IQ scores decreased by 2.502 when the UFCr level increased by 1.0 mg/L (β = −2.502, 95% confidence interval [CI]:−4.411, −0.593), and the possibility for having “excellent” intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group (P < 0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05). Conclusion:. Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.http://journals.lww.com/10.1097/CM9.0000000000002062
spellingShingle Zichen Feng
Ning An
Fangfang Yu
Jun Ma
Na Li
Yuhui Du
Meng Guo
Kaihong Xu
Xiangbo Hou
Zhiyuan Li
Guoyu Zhou
Yue Ba
Jing Ni
Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?
Chinese Medical Journal
title Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?
title_full Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?
title_fullStr Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?
title_full_unstemmed Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?
title_short Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?
title_sort do methylenetetrahydrofolate dehydrogenase cyclohydrolase and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school age children in areas of endemic fluorosis
url http://journals.lww.com/10.1097/CM9.0000000000002062
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