title: Modifying effect of COMT gene polymorphism and a predictive role for proteomics analysis in children's intelligence in endemic fluorosis area in Tianjin, 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.
authors.affiliation: *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.
authors.forename: Shun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: *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.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: *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.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: *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.
authors.forename: Weidong
authors.initials: W
authors.lastname: Qu
authors.affiliation: *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.
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Guan
authors.affiliation: *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.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: *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.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Jiang
authors.affiliation: *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.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: *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.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: *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.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Lei
authors.affiliation: *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.
authors.forename: Tao
authors.initials: T
authors.lastname: Xia
authors.affiliation: *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.
authors.forename: Zhenglun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: *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.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: *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.
authors.forename: Yihu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: *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.
authors.forename: Xue
authors.initials: X
authors.lastname: Wu
authors.affiliation: *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.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: *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.
authors.forename: Linyu
authors.initials: L
authors.lastname: Yu
authors.affiliation: *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.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Wang
mesh_terms: D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D002681:China / Q000453:epidemiology; D019353:Endemic Diseases; D005260:Female; D009050:Fluorosis, Dental / Q000453:epidemiology*; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D040901:Proteomics
chemical_list: D002394:Catechol O-Methyltransferase
keywords: COMT polymorphism; children’s IQ; fluoride; plasma proteomic