SLC1A2基因编码兴奋性氨基酸转运蛋白2(EAAT2),主要负责在中枢神经系统中将谷氨酸从突触间隙中重新吸收。谷氨酸是主要的兴奋性神经递质,EAAT2在维持神经元兴奋性和神经信号传导中起着关键作用。EAAT2的功能异常与多种神经系统疾病和神经精神疾病的发生发展密切相关。
最近的研究表明,SLC1A2基因的多态性与药物依赖性有关,可能导致神经疾病和精神疾病的发生。例如,一项研究发现,SLC1A2基因中rs4755404单核苷酸多态性(SNP)与冰毒依赖和冰毒诱导的精神病之间存在显著关联[1]。然而,另一项研究发现,SLC1A2基因的rs3794087变异与特发性震颤的风险之间没有关联[8]。
SLC1A2基因在癌症中也发挥重要作用。一项研究发现,在胃癌中,SLC1A2基因与CD44基因融合,导致SLC1A2转录失调,从而促进肿瘤生长和生存[2]。此外,SLC1A2基因融合在结直肠癌中也有发现,可能与结直肠癌的发生和发展有关[4]。
SLC1A2基因突变还与儿科神经系统疾病有关。一项研究发现,SLC1A2基因突变在沙特阿拉伯儿童中导致多种神经系统疾病,包括智力障碍、自闭症谱系障碍、癫痫等[3]。
SLC1A2基因在缺血性脑卒中中也发挥作用。一项研究发现,11-酮-β-乳香酸和Z-谷甾醇对缺血性脑卒中的协同作用与SLC1A2和Timp1基因的表达调控有关[5]。
此外,SLC1A2基因在乳腺癌脑转移中也发挥重要作用。一项研究发现,乳腺癌细胞分泌的miR-199b-5p可以劫持神经代谢偶联,通过SLC1A2基因的调控促进乳腺癌脑转移的发生[6]。
SLC1A2基因在精神疾病中也发挥重要作用。一项研究发现,SLC1A2基因的罕见变异与双相情感障碍和精神分裂症的易感性相关[7]。然而,另一项研究发现,SLC1A2基因与日本精神分裂症患者的遗传关联不显著[9]。
综上所述,SLC1A2基因在多种疾病中发挥重要作用,包括神经系统疾病、癌症和精神疾病。SLC1A2基因的功能异常可能导致神经递质失衡、细胞代谢紊乱和基因表达失调,从而影响疾病的发生和发展。深入研究SLC1A2基因的功能和调控机制,有助于开发针对相关疾病的个性化治疗策略,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Yahya, Dayang Nooreffazleen, Guad, Rhanye Mac, Wu, Yuan-Seng, Rashid, Rusdi Abdul, Sim, Maw Shin. 2023. SLC1A2 Gene Polymorphism Influences Methamphetamine-Induced Psychosis. In Journal of personalized medicine, 13, . doi:10.3390/jpm13020270. https://pubmed.ncbi.nlm.nih.gov/36836504/
2. Tao, Jiong, Deng, Nian Tao, Ramnarayanan, Kalpana, Palanisamy, Nallasivam, Tan, Patrick. . CD44-SLC1A2 gene fusions in gastric cancer. In Science translational medicine, 3, 77ra30. doi:10.1126/scitranslmed.3001423. https://pubmed.ncbi.nlm.nih.gov/21471434/
3. Mir, Ali, Almudhry, Montaha, Alghamdi, Fouad, Bashir, Shahid, Housawi, Yousef. 2021. SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population. In Human genetics, 141, 81-99. doi:10.1007/s00439-021-02404-x. https://pubmed.ncbi.nlm.nih.gov/34797406/
4. Shinmura, Kazuya, Kato, Hisami, Igarashi, Hisaki, Niwa, Hiroshi, Sugimura, Haruhiko. 2015. CD44-SLC1A2 fusion transcripts in primary colorectal cancer. In Pathology oncology research : POR, 21, 759-64. doi:10.1007/s12253-014-9887-2. https://pubmed.ncbi.nlm.nih.gov/25576211/
5. Liu, Tianlong, Bai, Min, Liu, Minna, Wen, Aidong, Ding, Yi. 2023. Novel synergistic mechanism of 11-keto-β-boswellic acid and Z-Guggulsterone on ischemic stroke revealed by single-cell transcriptomics. In Pharmacological research, 193, 106803. doi:10.1016/j.phrs.2023.106803. https://pubmed.ncbi.nlm.nih.gov/37230158/
6. Ruan, Xianhui, Yan, Wei, Cao, Minghui, Hevner, Robert F, Wang, Shizhen Emily. 2024. Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis. In Nature communications, 15, 4549. doi:10.1038/s41467-024-48740-0. https://pubmed.ncbi.nlm.nih.gov/38811525/
7. Fiorentino, Alessia, Sharp, Sally I, McQuillin, Andrew. 2014. Association of rare variation in the glutamate receptor gene SLC1A2 with susceptibility to bipolar disorder and schizophrenia. In European journal of human genetics : EJHG, 23, 1200-6. doi:10.1038/ejhg.2014.261. https://pubmed.ncbi.nlm.nih.gov/25406999/
8. Jiménez-Jiménez, Félix J, Alonso-Navarro, Hortensia, García-Martín, Elena, Agúndez, José A G. . SLC1A2 rs3794087 variant and risk for essential tremor: a systematic review and meta-analysis. In Pharmacogenetics and genomics, 25, 564-8. doi:10.1097/FPC.0000000000000171. https://pubmed.ncbi.nlm.nih.gov/26313486/
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