SCREENING AND VERIFICATION OF DIFFERENTIAL DNA METHYLATION GENES IN THE PERIPHERAL BLOOD CELLS OF CHILDREN WITH SKELETAL FLUOROSIS IN GUIZHOU PROVINCE OF CHINA.

The levels of DNA methylation were analyzed in the peripheral blood cells of children, with or without skeletal fluorosis, in the area of the coal-burning type of endemic fluorosis in Guizhou Province of China. Whole genome DNA methylation 450 K BeadChip and pyrosequencing were performed, and the main function and pathway of differential methylation genes determined by GO analysis and the KEGG database. The results showed that 15 differential hypermethylated and 22 hypomethylated CpG sites were determined in the children with skeletal fluorosis, which involved 29 known genes, as compared to controls. The majority of the differentially methylated CpG loci resided in the gene body. Further, the GO analysis and the KEGG database for the pathway analysis indicated that these differential genes are mainly involved in synapse maturation, axon, neuron projection membrane, transcription coactivator activity, and the Notch signaling pathway. Pyrosequencing analysis showed that the gene MAML2 was hypomethylated in the children with skeletal fluorosis, which is the same as the chip result. A change concerning genome-wide DNA methylation in the children with skeletal fluorosis was also found. The results suggest that the alteration of the hypomethylated MAML2 gene may play an important role in the occurrence and development of skeletal fluorosis. [ABSTRACT FROM AUTHOR]