SULT1A1,也称为Sulfotransferase Family 1A Member 1,是一种重要的药物和激素代谢酶,属于磺基转移酶超家族。SULT1A1参与代谢多种内源性和外源性乳腺致癌物质,其代谢活性受基因拷贝数变化的影响。研究表明,SULT1A1基因拷贝数变化与男性乳腺癌(MBC)的发生发展密切相关,BRCA2突变与SULT1A1基因缺失之间存在关联[1]。此外,SULT1A1基因表达受到NFI转录因子家族的调控,NFI-C和NFI-B的表达水平与SULT1A1表达呈正相关[2]。在亚洲人群中,SULT1A1 Arg213His(rs9282861)多态性与乳腺癌风险增加相关,尤其在医院为基础的、RFLP-PCR和高质量的研究中[3]。SULT1A1基因拷贝数差异对酶活性具有重要影响,个体间酶活性的差异可能部分归因于基因拷贝数差异[4]。此外,SULT1A1基因多态性与肺癌风险降低相关,尤其是在吸烟人群中[6]。在药物代谢方面,SULT1A1与CYP2D6共同参与他莫昔芬的代谢,SULT1A1基因型或拷贝数对他莫昔芬及其代谢产物的水平没有影响,但与N-脱甲基他莫昔芬/他莫昔芬和N-二脱甲基他莫昔芬/N-脱甲基他莫昔芬的比值相关[5]。
综上所述,SULT1A1基因在多种疾病中发挥重要作用,包括乳腺癌、肺癌等。SULT1A1基因拷贝数变化、基因多态性和基因表达调控与疾病风险密切相关。此外,SULT1A1还参与药物代谢,影响药物疗效。深入研究SULT1A1基因的功能和调控机制,有助于揭示疾病的发生发展机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Palli, Domenico, Rizzolo, Piera, Zanna, Ines, Tommasi, Stefania, Ottini, Laura. . SULT1A1 gene deletion in BRCA2-associated male breast cancer: a link between genes and environmental exposures? In Journal of cellular and molecular medicine, 17, 605-7. doi:10.1111/jcmm.12043. https://pubmed.ncbi.nlm.nih.gov/23711090/
2. Yao-Borengasser, Aiwei, Rogers, Lora J, Edavana, Vineetha K, Williams, Suzanne, Kadlubar, Susan A. 2014. Sulfotransferase 1A1 (SULT1A1) gene expression is regulated by members of the NFI transcription factors in human breast cancer cells. In BMC clinical pathology, 14, 1. doi:10.1186/1472-6890-14-1. https://pubmed.ncbi.nlm.nih.gov/24393253/
3. Forat-Yazdi, Mohammad, Jafari, Mohammadali, Kargar, Saeed, Foroughi, Elnaz, Neamatzadeh, Hossein. 2017. Association between SULT1A1 Arg213His (rs9282861) Polymorphism and Risk of Breast Cancer: A Systematic Review and Meta-Analysis. In Journal of research in health sciences, 17, e00396. doi:. https://pubmed.ncbi.nlm.nih.gov/29233949/
4. Hebbring, Scott J, Adjei, Araba A, Baer, Janel L, Weinshilboum, Richard M, Thibodeau, Stephen N. 2006. Human SULT1A1 gene: copy number differences and functional implications. In Human molecular genetics, 16, 463-70. doi:. https://pubmed.ncbi.nlm.nih.gov/17189289/
5. Gjerde, J, Hauglid, M, Breilid, H, Steen, V M, Lien, E A. 2007. Effects of CYP2D6 and SULT1A1 genotypes including SULT1A1 gene copy number on tamoxifen metabolism. In Annals of oncology : official journal of the European Society for Medical Oncology, 19, 56-61. doi:. https://pubmed.ncbi.nlm.nih.gov/17947222/
6. Walia, Harleen Kaur, Singh, Navneet, Sharma, Siddharth. 2021. Genetic polymorphism of Arg213His variant in the SULT1A1 gene is associated with reduced susceptibility to lung cancer in North Indian population. In Xenobiotica; the fate of foreign compounds in biological systems, 51, 1071-1080. doi:10.1080/00498254.2021.1963008. https://pubmed.ncbi.nlm.nih.gov/34328372/