{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMT2A functions as a pivotal regulator of cellular metal homeostasis, particularly for zinc, by binding metal ions and undergoing conformational transitions that govern zinc sequestration and release. Under both basal and oxidative stress conditions, MT2A can form disulfide bonds that facilitate additional zinc release, thereby modulating the activity of zinc‐dependent enzymes and antioxidant defenses. Its dynamic metal‐binding properties also enable the efficient trafficking of zinc to organelles such as mitochondria, which is essential for maintaining intracellular metabolic balance and protecting cells from metal‐induced toxicity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in metal regulation, MT2A critically influences cell survival pathways and the modulation of apoptosis and proliferation in various pathological settings. Aberrant MT2A expression has been shown to promote tumor cell invasion and chemoresistance through the upregulation of matrix metalloproteinases and modulation of transcription factors such as NF‐κB, while its downregulation can restore p53 folding and transcriptional activity, thereby inducing cell cycle arrest and apoptosis. Interactions with proteins such as ECRG2, HMBOX1, and PKCμ further underscore its multifaceted role in controlling growth and survival, ultimately contributing to the aggressiveness observed in certain cancers and providing a potential target for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMT2A’s protective roles extend to the modulation of heavy-metal toxicokinetics and the regulation of its own expression through genetic polymorphisms and transcriptional control, thereby impacting a spectrum of clinical conditions. Variants in the MT2A promoter have been associated with altered accumulation of toxic metals such as cadmium and lead in tissues—including the kidney, prostate, placenta, and vascular endothelium—and with consequent risks for type 2 diabetes, cardiovascular complications, renal dysfunction, and various cancers. Moreover, MT2A transcription is dynamically regulated by xenobiotic-responsive factors such as the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR), as well as by other modulators like myeloid zinc-finger 1 (MZF1) and XIAP-associated factor 1 (XAF1), which together fine-tune its expression in response to oxidative, inflammatory, and environmental stresses. 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"}, {"type": "b", "children": [{"type": "t", "text": "Metallothionein isoform 2A expression is inducible and protects against ROS-mediated cell death in rotenone-treated HeLa cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20051253"}], "href": "https://doi.org/10.1042/BJ20051253"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16402917"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16402917"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Eugenio Mocchegiani, Mario Muzzioli, Robertina Giacconi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metallothioneins/PARP-1/IL-6 interplay on natural killer cell activity in elderly: parallelism with nonagenarians and old infected humans. Effect of zinc supply."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mech Ageing Dev (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0047-6374(03)00023-x"}], "href": "https://doi.org/10.1016/s0047-6374(03"}, {"type": "t", "text": "00023-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12714254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12714254"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shu-Hua Chen, Liuxi Chen, David H Russell "}, {"type": "b", "children": [{"type": "t", "text": "Metal-induced conformational changes of human metallothionein-2A: a combined theoretical and experimental study of metal-free and partially metalated intermediates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Chem Soc (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/ja5047878"}], "href": "https://doi.org/10.1021/ja5047878"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24918957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24918957"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Antonia A Nemec, George D Leikauf, Bruce R Pitt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nickel mobilizes intracellular zinc to induce metallothionein in human airway epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2008-0409OC"}], "href": "https://doi.org/10.1165/rcmb.2008-0409OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19097988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19097988"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Leslie C Costello, Zhixin Guan, Renty B Franklin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metallothionein can function as a chaperone for zinc uptake transport into prostate and liver mitochondria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inorg Biochem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jinorgbio.2004.02.005"}], "href": "https://doi.org/10.1016/j.jinorgbio.2004.02.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15041247"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15041247"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yongping Cui, Jianbo Wang, Xinyu Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ECRG2, a novel candidate of tumor suppressor gene in the esophageal carcinoma, interacts directly with metallothionein 2A and links to apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(03)00122-0"}], "href": "https://doi.org/10.1016/s0006-291x(03"}, {"type": "t", "text": "00122-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12646258"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12646258"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "HanLin Ma, Le Su, HongWei Yue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HMBOX1 interacts with MT2A to regulate autophagy and apoptosis in vascular endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep15121"}], "href": "https://doi.org/10.1038/srep15121"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26456220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26456220"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Mutsushi Yamasaki, Takeo Nomura, Fuminori Sato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metallothionein is up-regulated under hypoxia and promotes the survival of human prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17914565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17914565"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Rosa Puca, Lavinia Nardinocchi, Gianluca Bossi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Restoring wtp53 activity in HIPK2 depleted MCF7 cells by modulating metallothionein and zinc."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2008.10.018"}], "href": "https://doi.org/10.1016/j.yexcr.2008.10.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18996371"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18996371"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Daina Lim, Koh Mei-Xin Jocelyn, George Wai-Cheong Yip, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Silencing the Metallothionein-2A gene inhibits cell cycle progression from G1- to S-phase involving ATM and cdc25A signaling in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2008.10.038"}], "href": "https://doi.org/10.1016/j.canlet.2008.10.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19062161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19062161"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Prema S Rao, Meena Jaggi, David J Smith, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metallothionein 2A interacts with the kinase domain of PKCmu in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2003.09.118"}], "href": "https://doi.org/10.1016/j.bbrc.2003.09.118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14550308"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14550308"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Kayoko Kita, Nobuhiko Miura, Minoru Yoshida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Potential effect on cellular response to cadmium of a single-nucleotide A --> G polymorphism in the promoter of the human gene for metallothionein IIA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-006-0238-6"}], "href": "https://doi.org/10.1007/s00439-006-0238-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16927099"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16927099"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Wanli Xue, Qiuqu Liu, Lu Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stable overexpression of human metallothionein-IIA in a heart-derived cell line confers oxidative protection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Lett (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.toxlet.2009.03.007"}], "href": "https://doi.org/10.1016/j.toxlet.2009.03.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19433272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19433272"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Robertina Giacconi, Catia Cipriano, Elisa Muti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel -209A/G MT2A polymorphism in old patients with type 2 diabetes and atherosclerosis: relationship with inflammation (IL-6) and zinc."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biogerontology (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10522-005-4907-y"}], "href": "https://doi.org/10.1007/s10522-005-4907-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16518702"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16518702"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Lina Yang, Hongyan Li, Ting Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in metallothionein-1 and -2 genes associated with the risk of type 2 diabetes mellitus and its complications."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Endocrinol Metab (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpendo.90234.2008"}], "href": "https://doi.org/10.1152/ajpendo.90234.2008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18349110"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18349110"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Zeliha Kayaaltı, Vugar Aliyev, Tülin Söylemezoğlu "}, {"type": "b", "children": [{"type": "t", "text": "The potential effect of metallothionein 2A -5A/G single nucleotide polymorphism on blood cadmium, lead, zinc and copper levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Appl Pharmacol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.taap.2011.06.023"}], "href": "https://doi.org/10.1016/j.taap.2011.06.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21767559"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21767559"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Yuanming Pan, Jiaqiang Huang, Rui Xing, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metallothionein 2A inhibits NF-κB pathway activation and predicts clinical outcome segregated with TNM stage in gastric cancer patients following radical resection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1479-5876-11-173"}], "href": "https://doi.org/10.1186/1479-5876-11-173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23870553"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23870553"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Bozena Werynska, Bartosz Pula, Beata Muszczynska-Bernhard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metallothionein 1F and 2A overexpression predicts poor outcome of non-small cell lung cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Pathol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexmp.2012.10.006"}], "href": "https://doi.org/10.1016/j.yexmp.2012.10.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23064051"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23064051"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Zeliha Kayaalti, Görkem Mergen, Tülin Söylemezoğlu "}, {"type": "b", "children": [{"type": "t", "text": "Effect of metallothionein core promoter region polymorphism on cadmium, zinc and copper levels in autopsy kidney tissues from a Turkish population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Appl Pharmacol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.taap.2010.03.007"}], "href": "https://doi.org/10.1016/j.taap.2010.03.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20303360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20303360"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Scott C Wesselkamper, Susan A McDowell, Mario Medvedovic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of metallothionein in the pathogenesis of acute lung injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2005-0248OC"}], "href": "https://doi.org/10.1165/rcmb.2005-0248OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16166738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16166738"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Anna Krześlak, Ewa Forma, Paweł Jóźwiak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metallothionein 2A genetic polymorphisms and risk of ductal breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10238-012-0215-4"}], "href": "https://doi.org/10.1007/s10238-012-0215-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23053628"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23053628"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Shoko Sato, Hitoshi Shirakawa, Shuhei Tomita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Appl Pharmacol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.taap.2013.08.017"}], "href": "https://doi.org/10.1016/j.taap.2013.08.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23994556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23994556"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Shuye Lin, Xiaoyue Wang, Yuanming Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcription Factor Myeloid Zinc-Finger 1 Suppresses Human Gastric Carcinogenesis by Interacting with Metallothionein 2A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-18-1281"}], "href": "https://doi.org/10.1158/1078-0432.CCR-18-1281"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30301827"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30301827"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Anna Krześlak, Ewa Forma, Grażyna Chwatko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of metallothionein 2A gene polymorphism on allele-specific gene expression and metal content in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Appl Pharmacol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.taap.2013.02.013"}], "href": "https://doi.org/10.1016/j.taap.2013.02.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23466427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23466427"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Deniz Tekin, Zeliha Kayaaltı, Vugar Aliyev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The effects of metallothionein 2A polymorphism on placental cadmium accumulation: Is metallothionein a modifiying factor in transfer of micronutrients to the fetus?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Appl Toxicol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jat.1661"}], "href": "https://doi.org/10.1002/jat.1661"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21328412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21328412"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Cheol-Hee Shin, Min-Goo Lee, Jikhyon Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of XAF1-MT2A mutual antagonism as a molecular switch in cell-fate decisions under stressful conditions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1700861114"}], "href": "https://doi.org/10.1073/pnas.1700861114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28507149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28507149"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Deniz Tekin, Zeliha Kayaaltı, Tülin Söylemezoğlu "}, {"type": "b", "children": [{"type": "t", "text": "The effects of metallothionein 2A polymorphism on lead metabolism: are pregnant women with a heterozygote genotype for metallothionein 2A polymorphism and their newborns at risk of having higher blood lead levels?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Arch Occup Environ Health (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00420-011-0711-y"}], "href": "https://doi.org/10.1007/s00420-011-0711-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22005883"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22005883"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Di Liu, Meng Wang, Tian Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic polymorphisms (rs10636 and rs28366003) in metallothionein 2A increase breast cancer risk in Chinese Han population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.101177"}], "href": "https://doi.org/10.18632/aging.101177"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28228606"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28228606"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Zeliha Kayaalti, Tülin Söylemezoğlu "}, {"type": "b", "children": [{"type": "t", "text": "The polymorphism of core promoter region on metallothionein 2A-metal binding protein in Turkish population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-009-9586-3"}], "href": "https://doi.org/10.1007/s11033-009-9586-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19572214"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19572214"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Ana Martinho, Isabel Gonçalves, Isabel Cardoso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human metallothioneins 2 and 3 differentially affect amyloid-beta binding by transthyretin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1742-4658.2010.07749.x"}], "href": "https://doi.org/10.1111/j.1742-4658.2010.07749.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20646067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20646067"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Zeliha Kayaaltı, Levent Sahiner, M Emre Durakoğlugil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distributions of interleukin-6 (IL-6) promoter and metallothionein 2A (MT2A) core promoter region gene polymorphisms and their associations with aging in Turkish population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Gerontol Geriatr (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.archger.2011.01.001"}], "href": "https://doi.org/10.1016/j.archger.2011.01.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21277639"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21277639"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Chen-Cheng Yang, Chih-Shien Chuang, Chia-I Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The association of the blood lead level and serum lipid concentrations may be modified by the genetic combination of the metallothionein 2A polymorphisms rs10636 GC and rs28366003 AA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Lipidol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jacl.2016.12.010"}], "href": "https://doi.org/10.1016/j.jacl.2016.12.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28391890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28391890"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Kelly Christine Marques Fernandes, Airton Cunha Martins, Andréia Ávila Soares de Oliveira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphism of Metallothionein 2A Modifies Lead Body Burden in Workers Chronically Exposed to the Metal."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Public Health Genomics (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000441713"}], "href": "https://doi.org/10.1159/000441713"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26594907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26594907"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Yuta Hattori, Mariko Naito, Masahiko Satoh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metallothionein MT2A A-5G Polymorphism as a Risk Factor for Chronic Kidney Disease and Diabetes: Cross-Sectional and Cohort Studies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/toxsci/kfw080"}], "href": "https://doi.org/10.1093/toxsci/kfw080"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27122239"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27122239"}]}]}]}