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Toxicol Sci. 2015 Apr;144(2):238-45. doi: 10.1093/toxsci/kfu311. Epub 2015 Jan 1.

Modifying effect of COMT gene polymorphism and a predictive role for proteomics analysis in children's intelligence in endemic fluorosis area in Tianjin, China.

Author information

1
*Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, Tianjin Center for Disease Control and Prevention, Tianjin 300011, Tianjin, Department of Environmental Health and MOE Key Lab of Public Health and Safety, School of Public Health, Fudan University, Shanghai 200032, Shanghai and Department of Pathology, Guiyang Medical College, Guiyang 550004, Guizhou, People's Republic of China wangaiguo@mails.tjmu.edu.cn.
2
*Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, Tianjin Center for Disease Control and Prevention, Tianjin 300011, Tianjin, Department of Environmental Health and MOE Key Lab of Public Health and Safety, School of Public Health, Fudan University, Shanghai 200032, Shanghai and Department of Pathology, Guiyang Medical College, Guiyang 550004, Guizhou, People's Republic of China.

Abstract

Cumulative fluoride exposure has adverse influences on children's intelligence quotient (IQ). In addition, catechol-O-methyltransferase (COMT) gene Val158Met polymorphism (rs4680) is associated with cognitive performance. This study aimed to evaluate the associations of COMT polymorphism and alterations of protein profiles with children's intelligence in endemic fluorosis area. We recruited 180 schoolchildren (10-12 years old) from high fluoride exposure (1.40 mg/l) and control areas (0.63 mg/l) in Tianjin City, China. The children's IQ, fluoride contents in drinking water (W-F), serum (S-F), and urine (U-F); serum thyroid hormone levels, COMT Val158Met polymorphism, and plasma proteomic profiling were determined. Significant high levels of W-F, S-F, U-F, along with poor IQ scores were observed in the high fluoride exposure group compared with those in control (all P < 0.05). S-F and U-F were inversely related with IQ (r(s) = -0.47, P < 0.01; r(s) = -0.45, P = 0.002). Importantly, higher fluoride exposure was associated with steeper cognitive decline among children with the reference allele Val compared with those homozygous or heterozygous for the variant allele Met (95% CI, -16.80 to 2.55; P interaction < 0.01). Additionally, 5 up-regulated protein spots related to cell immunity and metabolism were detected in children with high fluoride exposure compared with the control. In conclusion, fluoride exposure was adversely associated with children's intelligence, whereas the COMT polymorphism may increase the susceptibility to the deficits in IQ due to fluoride exposure. Moreover, the proteomic analysis can provide certain basis for identifying the early biological markers of fluorosis among children.

KEYWORDS:

COMT polymorphism; children’s IQ; fluoride; plasma proteomic

PMID:
25556215
DOI:
10.1093/toxsci/kfu311
[Indexed for MEDLINE]

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