Polymorphisms of the AS3MT gene are associated with arsenic methylation capacity and damage to the P21 gene in arsenic trioxide plant workers
Polymorphisms of the AS3MT gene are associated with arsenic methylation capacity and damage to the P21 gene in arsenic trioxide plant workers
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AS3MT 基因多态性与三氧化二砷工厂工人砷甲基化能力和 P21 基因损伤有关
DOI：
10.1177/07482337211013321
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发表时间：
2021-11
影响因子：
1.9
通讯作者：
He Yuefeng
中科院分区：
文献类型：
--
作者：
Guanghui Ni;Tan Jingwen;Wang Mengjie;Ping Nina;Min Liu;He Yuefeng
流行病学证据表明，暴露于砷（As）的每个个体的代谢特征与癌症、冠心病和糖尿病的风险有关。砷甲基转移酶（AS3MT）基因在砷代谢中起关键作用。AS3MT基因的几个单核苷酸多态性可能影响酶活性和基因转录。AS3MT基因多态性与尿中甲基砷酸（MMA）和二甲基砷酸（DMA）的比例以及癌症的发病率相关。P21蛋白是一种细胞周期蛋白依赖性激酶抑制剂。P21基因的突变已在癌症患者中发现。在我们的研究中，我们调查是否AS3MT基因的多态性改变作为甲基化能力和不利影响P21基因在三氧化二砷工厂工人。定量聚合酶链反应检测DNA损伤。采用限制性片段长度多态性分析方法分析AS3MT基因的基因型。结果表明，高浓度砷暴露的个体P21基因片段DNA损伤更大。P21基因片段的DNA损伤程度与尿中MMA含量呈显著正相关。然而，P21基因片段的DNA损伤与尿中DMA百分比（%uDMA）、初级甲基化指数（PMI）和次级甲基化指数呈负相关。我们发现，具有rs7085104 GG或GA等位基因的受试者与较高的%uDMA和PMI以及较少的DNA损伤相关。携带rs11191454 GG+GA或GA等位基因的受试者也与较高的%uDMA和PMI和较少的DNA损伤相关。我们的研究结果表明，在AS3MT基因的rs1191454和rs7085104影响砷诱导的DNA损伤，通过改变个人的代谢效率。
Epidemiological evidence suggests that the metabolic profiles of each individual exposed to arsenic (As) are related to the risk of cancer, coronary heart disease, and diabetes. The arsenite methyltransferase (AS3MT) gene plays a key role in As metabolism. Several single nucleotide polymorphisms in the AS3MT gene may affect both enzyme activity and gene transcription. AS3MT polymorphisms are associated with the proportions of monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA) in urine as well as the incidence of cancer. P21 protein is a cyclin-dependent kinase inhibitor. Mutations of the P21 gene have been found in cancer patients. In our study, we investigate whether polymorphisms of the AS3MT gene alter As methylation capacity and adversely affect the P21 gene in arsenic trioxide plant workers. The DNA damage was examined by the quantitative polymerase chain reaction. Restriction fragment length polymorphism was used to analyze the genotype of the AS3MT gene. The results showed that DNA damage in P21 gene fragments was greater in those individuals exposed to high levels of As. There was a strong positive correlation between the DNA damage to P21 gene fragments and the percentage of MMA in urine. However, DNA damage in P21 gene fragments was negatively associated with the percentage of DMA in urine (%uDMA), primary methylation index (PMI), and secondary methylation index. We found that subjects with the rs7085104 GG or GA allele were associated with higher %uDMA and PMI and less DNA damage. The subjects with the rs11191454 GG+GA or GA allele were also associated with higher %uDMA and PMI and less DNA damage. Our results suggest that rs1191454 and rs7085104 in the AS3MT gene affect the As-induced DNA damage by altering individual metabolic efficiency.
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影响因子：
3.4
作者：
Ozen, Alaattin;Kocak, Zafer;Karagol, Hakan
通讯作者：
Karagol, Hakan
砷甲基化及代谢对砷相关皮损变化的影响
影响因子：
5.8
作者：
Wei Binggan;Yu Jiangping;Kong Chang;Li Hairong;Yang Linsheng;Xia Yajuan;Wu Kegong
通讯作者：
Wu Kegong
DOI：
10.1016/j.mrfmmm.2008.07.003
发表时间：
2009-07-10
影响因子：
2.3
作者：
Engstrom, Karin Schlawicke;Nermell, Barbro;Broberg, Karin
通讯作者：
Broberg, Karin
影响因子：
10.4
作者：
Tajuddin SM;Amaral AF;Fernández AF;Rodríguez-Rodero S;Rodríguez RM;Moore LE;Tardón A;Carrato A;García-Closas M;Silverman DT;Jackson BP;García-Closas R;Cook AL;Cantor KP;Chanock S;Kogevinas M;Rothman N;Real FX;Fraga MF;Malats N;Spanish Bladder Cancer/EPICURO Study Investigators
通讯作者：
Spanish Bladder Cancer/EPICURO Study Investigators
影响因子：
4.5
作者：
Vahter, M
通讯作者：
Vahter, M