Abstract

Highlights

  • High fluoride water consumption increases cholinergic enzymes activity significantly.
  • High fluoride water chronic consumption increases the risk of systemic inflammation.
  • Involvement of anti-cholinergic pathway for inflammation is speculated.
  • ACHE gene SNPs (rs 2571598, rs17228602) & BCHE rs 1803274 associated with fluorosis

Fluoride is one of the abundant elements found in the Earth’s crust and is a global environmental issue. The present work aimed to find the impact of chronic consumption of fluoride contained groundwater on human subjects. Five hundred and twelve volunteers from different areas of Pakistan were recruited. Cholinergic status, acetylcholinesterase and butyrylcholinesterase gene SNPs and pro-inflammatory cytokines were examined. Association analysis, regression and other standard statistical analyses were performed. Physical examination of the fluoride endemic areas’ participants revealed the symptoms of dental and skeletal fluorosis. Cholinergic enzymes (AChE and BChE) were significantly increased among different exposure groups. ACHE gene 3?-UTR variant and BCHE K-variant showed a significant association with risk of fluorosis. Pro-inflammatory cytokines (TNF-?, IL-1? and IL-6) were found to be increased and have a significant correlation in response to fluoride exposure and cholinergic enzymes. The study concludes that chronic consumption of high fluoride-contained water is a risk factor for developing low-grade systemic inflammation through the cholinergic pathway and the studied cholinergic gene SNPs were identified to be associated with the risk of fluorosis.

*Original full-text article online at: https://www.sciencedirect.com/science/article/abs/pii/S0048969723019782