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Sci Rep. 2017 Jan 12;7:40086. doi: 10.1038/srep40086.

Matrix Metallopeptidase-2 Gene rs2287074 Polymorphism is Associated with Brick Tea Skeletal Fluorosis in Tibetans and Kazaks, China.

Pei J1,2, Li B1,2, Liu Y1,2, Liu X1,2, Li M1,2, Chu Y1,2, Yang Q1,2, Jiang W1,2, Chen F1,2, Darko GM1,2, Yang Y1,2, Gao Y1,2.

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Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150081, Heilongjiang Province, China.
Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province &Ministry of Health (23618504), Harbin Medical University, Harbin 150081, Heilongjiang Province, China.


Brick tea skeletal fluorosis is still a public health issue in the north-western area of China. However its pathogenesis remains unknown. Our previous study reveals that the severity of skeletal fluorosis in Tibetans is more serious than that in Kazaks, although they have similar fluoride exposure, suggesting the onset of brick tea type skeletal fluorosis might be genetically influenced. Here we show that MMP-2 rs2287074 SNP (G/A), but not rs243865, was associated with Brick tea type fluorosis in Tibetans and Kazaks, China. The trend test reveals a decline in probability for skeletal fluorosis with increasing number of A alleles in Tibetans. After controlling potential confounders, AA genotype had about 80 percent lower probability of developing skeletal fluorosis than GG genotype in Tibetans (odds ratio = 0.174, 95% CI: 0.053, 0.575), and approximately 53 percent lower probability in Kazaks (odds ratio = 0.462, 95% CI: 0.214, 0.996). A meta-analysis shows that the AA genotype had approximately 63 percent lower odds (odds ratio = 0.373, 95% CI: 0.202, 0.689) compared with GG genotype within the two ethnicities. A significant correlation was also found between the genotype of MMP2 rs2287074 and skeletal fluorosis severity. Therefore, the A allele of MMP2 rs2287074 could be a protective factor for brick tea skeletal fluorosis.

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