Matrix Metallopeptidase-2 Gene rs2287074 Polymorphism is Associated with Brick Tea Skeletal Fluorosis in Tibetans and Kazaks, China.
Matrix Metallopeptidase-2 Gene rs2287074 Polymorphism is Associated with Brick Tea Skeletal Fluorosis in Tibetans and Kazaks, China.
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DOI：
10.1038/srep40086
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发表时间：
2017-01-12
影响因子：
4.6
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Pei J;Li B;Liu Y;Liu X;Li M;Chu Y;Yang Q;Jiang W;Chen F;Darko GM;Yang Y;Gao Y
砖茶氟骨症仍然是中国西北地区的一个公共卫生问题。然而其发病机制仍不清楚。我们之前的研究表明，藏族氟骨症的严重程度比哈萨克族更严重，尽管他们的氟化物暴露程度相似，这表明砖茶型氟骨症的发病可能受到遗传影响。在这里，我们发现 MMP-2 rs2287074 SNP (G/A)，而不是 rs243865，与中国藏族和哈萨克族的砖茶型氟中毒相关。趋势检验显示，随着藏族人中A等位基因数量的增加，氟骨症的概率下降。在控制了潜在的混杂因素后，在藏族中，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% CI：0.053，0.575），在哈萨克族中，AA基因型患氟骨症的概率比GG基因型低约53%（比值比 = 0.462，95% CI： 0.214、0.996）。荟萃分析显示，两个种族中，AA 基因型的比值比 GG 基因型低约 63%（比值比 = 0.373，95% CI：0.202，0.689）。 MMP2 rs2287074 基因型与氟骨症严重程度之间也存在显着相关性。因此，MMP2 rs2287074的A等位基因可能是砖茶氟骨症的保护因素。
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.