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.
Sci Rep. 2017 Jan 12;7:40086. doi: 10.1038/srep40086.
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.
砖茶型氟骨症在中国西北地区仍然是一个公共卫生问题。然而，其发病机制尚不清楚。我们之前的研究表明，藏族人群的氟骨症严重程度比哈萨克族更为严重，尽管他们有相似的氟暴露，这表明砖茶型氟骨症的发病可能受到遗传因素的影响。在这里，我们发现 MMP-2 rs2287074 SNP（G/A）而非 rs243865 与中国藏族和哈萨克族的砖茶型氟骨症有关。趋势检验显示，随着 A 等位基因数量的增加，藏族人群患氟骨症的概率呈下降趋势。在控制潜在混杂因素后，AA 基因型患氟骨症的概率比 GG 基因型低约 80%（比值比=0.174，95%可信区间：0.053，0.575），在哈萨克族中低约 53%（比值比=0.462，95%可信区间：0.214，0.996）。Meta 分析表明，与 GG 基因型相比，AA 基因型患氟骨症的几率降低了约 63%（比值比=0.373，95%可信区间：0.202，0.689）。MMP2 rs2287074 的基因型与氟骨症严重程度之间也存在显著相关性。因此，MMP2 rs2287074 的 A 等位基因可能是砖茶型氟骨症的保护因素。
