Aquaporin 5 Interacts with Fluoride and Possibly Protects against Caries

Aquaporins (AQP) are water channel proteins and the genes coding for AQP2, AQP5, and AQP6 are clustered in 12q13. Since AQP5 is expressed in serous acinar cells of salivary glands, we investigated its involvement in caries. DNA samples from 1,383 individuals from six groups were studied. Genotypes of eight single nucleotide polymorphisms covering the aquaporin locus were tested for association with caries experience. Interaction with genes involved in enamel formation was tested. The association between enamel microhardness at baseline, after creation of artificial caries lesion, and after exposure to fluoride and the genetic markers in AQP5 was tested. Finally, AQP5 expression in human whole saliva, after exposure to fluoride in a mammary gland cell line, which is known to express AQP5, and in Wistar rats was also verified. Nominal associations were found between caries experience and markers in the AQP5 locus. Since these associations suggested that AQP5 may be inhibited by levels of fluoride in the drinking water that cause fluorosis, we showed that fluoride levels above optimal levels change AQP5 expression in humans, cell lines, and rats. We have shown that AQP5 is involved in the pathogenesis of caries and likely interacts with fluoride.

水通道蛋白（Aquaporin, AQP）是一类水通道蛋白，编码AQP2、AQP5及AQP6的基因簇定位于12q13染色体区域。鉴于AQP5在唾液腺浆液性腺泡细胞中表达，本研究探讨了其在龋病发生发展中的作用。本研究纳入6组共1383名个体的DNA样本，对覆盖水通道蛋白基因座的8个单核苷酸多态性（single nucleotide polymorphism, SNP）位点进行基因分型，以分析其与龋病患病经历的关联；同时检测了与牙釉质形成相关基因的互作效应。此外，本研究分别检测了基线状态、人工龋损形成后、经氟化物处理后的牙釉质微硬度，以及AQP5基因座内的遗传标记与上述指标的关联。最后，本研究验证了AQP5在人类全唾液、已知表达AQP5的乳腺细胞系经氟化物处理后，以及Wistar大鼠体内的表达情况。研究发现龋病患病经历与AQP5基因座内的遗传标记存在名义关联；鉴于此类关联提示饮用水中引发氟中毒的氟化物水平可能抑制AQP5，本研究进一步证实，高于最优浓度的氟化物可在人类、细胞系及大鼠体内改变AQP5的表达。综上，本研究表明AQP5参与龋病的发病机制，且可能与氟化物存在相互作用。