Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy.
Genetic Variants and Protein Alterations of Selenium- and T-2 Toxin-Responsive Genes Are Associated With Chondrocytic Damage in Endemic Osteoarthropathy.
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硒和 T-2 毒素反应基因的遗传变异和蛋白质改变与地方性骨关节病的软骨细胞损伤相关
DOI：
10.3389/fgene.2021.773534
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发表时间：
2021
影响因子：
3.7
通讯作者：
Guo X
中科院分区：
文献类型：
--
作者：
Ning Y;Hu M;Diao J;Gong Y;Huang R;Chen S;Zhang F;Liu Y;Chen F;Zhang P;Zhao G;Chang Y;Xu K;Zhou R;Li C;Zhang F;Lammi M;Wang X;Guo X
环境因素在大骨节病发病中的作用机制尚不清楚。我们的目的是确定单核苷酸多态性（SNPs）和蛋白质改变的硒和T-2毒素反应基因，提供新的证据，软骨细胞损伤大骨节病。本研究采集了258名受试者的肘静脉血，其中包括129名性别匹配的大骨节病患者和129名健康对照者，进行SNP检测。我们应用加性模型、显性模型和隐性模型来识别显著的SNP。然后，我们使用比较毒理基因组学数据库（CTD）选择硒和T-2毒素反应基因的候选SNP位点。最后，应用免疫组织化学方法验证候选基因在15名受试者（包括5名大骨节病，5名骨关节炎（OA）和5名健康对照）的膝关节软骨中的蛋白表达。在本研究中，对49个SNP进行了基因分型。rs6494629的C等位基因在大骨节病组中的频率低于对照组（OR = 0.63，p = 0.011）。基于CTD数据库，PPARG、ADAM 12、IL 6、SMAD 3和TIMP 2被鉴定为与硒、亚硒酸钠和T-2毒素相互作用。PPARG基因rs 12629751与大骨节病的发病有显著相关性（加性模型：OR = 0.46，p = 0.012;显性模型：OR = 0.45，p = 0.049;隐性模型：OR = 0.18，p = 0.018），ADAM 12的rs 1871054（优势模型：OR = 2.19，p = 0.022），IL 6的rs 1800796（显性模型：OR = 0.30，p = 0.003），SMAD 3的rs6494629（加性模型：OR = 0.65，p = 0.019;显性模型：OR = 0.52，p = 0.012）和TIMP 2的rs 4789936（隐性模型：OR = 5.90，p = 0.024）。免疫组化证实，与OA和正常对照相比，大骨节病患者的PPARG、ADAM 12、SMAD 3和TIMP 2显著上调（p < 0.05）。PPARG、ADAM 12、SMAD 3和TIMP 2基因多态性可能与大骨节病的发病风险有关。这些基因可能通过干扰细胞外基质的稳态而促进大骨节病的发病。
The mechanism of environmental factors in Kashin–Beck disease (KBD) remains unknown. We aimed to identify single nucleotide polymorphisms (SNPs) and protein alterations of selenium- and T-2 toxin–responsive genes to provide new evidence of chondrocytic damage in KBD. This study sampled the cubital venous blood of 258 subjects including 129 sex-matched KBD patients and 129 healthy controls for SNP detection. We applied an additive model, a dominant model, and a recessive model to identify significant SNPs. We then used the Comparative Toxicogenomics Database (CTD) to select selenium- and T-2 toxin–responsive genes with the candidate SNP loci. Finally, immunohistochemistry was applied to verify the protein expression of candidate genes in knee cartilage obtained from 15 subjects including 5 KBD, 5 osteoarthritis (OA), and 5 healthy controls. Forty-nine SNPs were genotyped in the current study. The C allele of rs6494629 was less frequent in KBD than in the controls (OR = 0.63, p = 0.011). Based on the CTD database, PPARG, ADAM12, IL6, SMAD3, and TIMP2 were identified to interact with selenium, sodium selenite, and T-2 toxin. KBD was found to be significantly associated with rs12629751 of PPARG (additive model: OR = 0.46, p = 0.012; dominant model: OR = 0.45, p = 0.049; recessive model: OR = 0.18, p = 0.018), rs1871054 of ADAM12 (dominant model: OR = 2.19, p = 0.022), rs1800796 of IL6 (dominant model: OR = 0.30, p = 0.003), rs6494629 of SMAD3 (additive model: OR = 0.65, p = 0.019; dominant model: OR = 0.52, p = 0.012), and rs4789936 of TIMP2 (recessive model: OR = 5.90, p = 0.024). Immunohistochemistry verified significantly upregulated PPARG, ADAM12, SMAD3, and TIMP2 in KBD compared with OA and normal controls (p < 0.05). Genetic polymorphisms of PPARG, ADAM12, SMAD3, and TIMP2 may contribute to the risk of KBD. These genes could promote the pathogenesis of KBD by disturbing ECM homeostasis.
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DOI：
10.1002/jbmr.2287
发表时间：
2014-12
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Chen H;Ghori-Javed FY;Rashid H;Adhami MD;Serra R;Gutierrez SE;Javed A
通讯作者：
Javed A
源自 TIMP2 的环状 RNA 作为竞争性内源性 RNA，通过靶向 miR-185-5p 和基质金属蛋白酶 2 调节椎间盘退变
影响因子：
5.4
作者：
Guo, Wei;Zhang, Bin;Cui, Qing
通讯作者：
Cui, Qing
影响因子：
1.5
作者：
Ding Zheru;Fu Peiliang;Fu Qiwei
通讯作者：
Fu Qiwei
影响因子：
5.5
作者：
He, Ying;Fan, Lihong;Chen, Jinghong
通讯作者：
Chen, Jinghong
影响因子：
6.2
作者：
Kveiborg, Marie;Albrechtsen, Reidar;Wewer, Ulla M.
通讯作者：
Wewer, Ulla M.