FRZB1 rs2242070 polymorphisms is associated with brick tea type skeletal fluorosis in Kazakhs, but not in Tibetans, China.

Skeletal fluorosis is a metabolic bone and joint disease caused by excessive accumulation of fluoride in the bones. Compared with Kazakhs, Tibetans are more likely to develop moderate and severe brick tea type skeletal fluorosis, although they have similar fluoride exposure. Single nucleotide polymorphisms (SNPs) in frizzled-related protein (FRZB) have been associated with osteoarthritis, but their association with the risk of skeletal fluorosis has not been reported. In this paper, we investigated the association of three SNPs (rs7775, rs2242070 and rs9288087) in FRZB1with brick tea type skeletal fluorosis risk in a cross-sectional case-control study conducted in Sinkiang and Qinghai, China. A total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled in this study, in which cases and controls were 221 and 377, respectively. The skeletal fluorosis was diagnosed according to the Chinese diagnostic criteria of endemic skeletal fluorosis (WS192-2008). The fluoride content in tea water or urine was detected using the fluoride ion electrode. SNPs were assessed using the Sequenom MassARRAY system. Binary logistic regressions found evidence of association with rs2242070 AA genotype in only Kazakh participants [odds ratio (OR) 0.417, 95% CI 0.216-0.807, p = 0.009], but not in Tibetans. When stratified by age, this protective effect of AA genotype in rs2242070 was pronounced in Kazakh participants aged 46-65 (OR 0.321, 95% CI 0.135-0.764, p = 0.010). This protective association with AA genotype in rs2242070 in Kazakhs also appeared to be stronger with tea fluoride intake > 3.5 mg/day (OR 0.396, 95% CI 0.182-0.864, p = 0.020). Our data suggest there might be differential genetic influence on skeletal fluorosis risk in Kazakh and Tibetan participants and that this difference might be modified by tea fluoride intake.

Autophagy May Be Involved in Fluoride-Induced Learning Impairment in Rats.

Fluoride can induce neurotoxicity, but the mechanism is not clear. In this study, we explored the role of autophagy in F--induced neurotoxicity of Wistar rats. Eighty Wistar rats were randomly divided into four groups: the control group (distilled water containing less than 0.1 mg/L F-) and three NaF-treated groups (F- was respectively administered at 25, 50, and 100 mg/L orally via drinking water). The water maze experiment showed that NaF exposure impaired the learning capabilities of the rats. When compared with the control group, the mean escape latency of the rats in the 100 mg/L F- group was much longer (P < 0.05). Immunohistochemical analysis showed that NaF exposure induced autophagy, as shown by the significant increase of Beclin-1 expression in the hippocampal CA1 region and DG region. Transmission electron microscopy was used to observe the ultrastructural changes of hippocampal neurons. With the increase of F- concentration, the ultrastructural abnormalities of hippocampal neurons increased. These results indicate that fluoride can impair the learning ability of rats, which may be related to the induction of autophagy in rat hippocampal neurons.