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.

This study aimed to investigate the effects of drinking water with high concentrations of iodine on the intelligence of children in Tianjin, China. It was a population-based health survey utilizing a random cluster sampling design conducted in June 2005. Participants were recruited from the total population of primary school children attending years 1–4 with ages ranging from 8 to 10 years. Intelligence quotient (IQ) was assessed using the combined Raven's test, second edition. Linear regression analyses were applied to test for any association between water iodine concentration and IQ. A total of 1229 students were recruited with a mean IQ of 105.8 (95% CI: 104.2–107.3). Water analyses indicated iodine concentrations were high in one rural region and exceedingly high in another with median values of 137.5 and 234.7 µg/l, respectively. There was a significant association between residing in the very high water iodine region and a reduction of IQ by an average of about nine points (P = 0.022), after adjusting for the potential confounding factors. Exposure to high iodine concentrations in drinking water has detrimental effects on the intelligence of children.