TCF7L2,也称为转录因子7样2,是一种编码转录因子的基因。转录因子是一类能够结合DNA并调控基因表达的蛋白质,它们在细胞的生长、分化、发育和代谢等生物学过程中发挥着重要作用。TCF7L2基因位于人类2号染色体上,其编码的蛋白质在Wnt信号通路中发挥着重要作用,Wnt信号通路是一种保守的信号通路,在动物发育过程中调控细胞命运和器官形成。TCF7L2蛋白与β-连环蛋白相互作用,共同调控下游基因的表达。此外,TCF7L2还与其他转录因子和DNA结合蛋白相互作用,参与调控细胞的增殖、分化和凋亡等过程。
TCF7L2基因的多态性与多种疾病的发生发展相关。其中,最显著的是与2型糖尿病(T2DM)的关联。多项研究发现,TCF7L2基因的某些单核苷酸多态性(SNPs)与T2DM的易感性相关。例如,rs7903146、rs12255372等位点多态性与T2DM的发病风险显著相关[1,2,4,5,9]。此外,TCF7L2基因的多态性还与糖尿病的微血管和大血管并发症相关。例如,TCF7L2基因的某些SNPs与糖尿病肾病、心血管疾病等并发症的发病风险相关[4,5,6]。此外,TCF7L2基因的多态性还与结肠癌的发生发展相关。例如,rs6983267、rs7903146等位点多态性与结肠癌的易感性相关[7,8]。此外,TCF7L2基因的多态性还与其他疾病相关,例如肾脏移植后新发糖尿病[3]。
综上所述,TCF7L2基因是一种重要的转录因子基因,其编码的蛋白质在Wnt信号通路中发挥着重要作用,参与调控细胞的生长、分化、发育和代谢等生物学过程。TCF7L2基因的多态性与多种疾病的发生发展相关,包括2型糖尿病、糖尿病并发症、结肠癌等。TCF7L2基因的研究有助于深入理解这些疾病的发病机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. He, Jingjing, Zhang, Meng, Ren, Jianhua, Jiang, Xiaolian. 2024. Correlation between TCF7L2 and CAPN10 gene polymorphisms and gestational diabetes mellitus in different geographical regions: a meta-analysis. In BMC pregnancy and childbirth, 24, 15. doi:10.1186/s12884-023-06177-1. https://pubmed.ncbi.nlm.nih.gov/38166877/
2. Tabikhanova, L E, Osipova, L P, Churkina, T V, Voronina, E N, Filipenko, M L. . TCF7L2 gene polymorphism in populations of f ive Siberian ethnic groups. In Vavilovskii zhurnal genetiki i selektsii, 26, 188-195. doi:10.18699/VJGB-22-23. https://pubmed.ncbi.nlm.nih.gov/35434484/
3. Helvaci, Özant, Korucu, Berfu, Yeter, Haci Hasan, Bali, Musa, Güz, Galip. 2021. TCF7L2 (rs7903146) But Not CDKAL1 (rs7754840) Gene Polymorphisms Increase the Risk of New-Onset Diabetes After Kidney Transplant. In Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 21, 872-878. doi:10.6002/ect.2020.0335. https://pubmed.ncbi.nlm.nih.gov/33641658/
4. Aboelkhair, Noran Talaat, Kasem, Heba Elsayed, Abdelmoaty, Amera Anwar, El-Edel, Rawhia Hassan. 2021. TCF7L2 gene polymorphism as a risk for type 2 diabetes mellitus and diabetic microvascular complications. In Molecular biology reports, 48, 5283-5290. doi:10.1007/s11033-021-06537-0. https://pubmed.ncbi.nlm.nih.gov/34232465/
5. Rattanatham, Rujikorn, Settasatian, Nongnuch, Komanasin, Nantarat, Senthong, Vichai, Settasatian, Chatri. 2021. Association of Combined TCF7L2 and KCNQ1 Gene Polymorphisms with Diabetic Micro- and Macrovascular Complications in Type 2 Diabetes Mellitus. In Diabetes & metabolism journal, 45, 578-593. doi:10.4093/dmj.2020.0101. https://pubmed.ncbi.nlm.nih.gov/33752320/
6. Satirapoj, Bancha, Tasanavipas, Pamila, Supasyndh, Ouppatham. 2019. Role of TCF7L2 and PPARG2 Gene Polymorphisms in Renal and Cardiovascular Complications among Patients with Type 2 Diabetes: A Cohort Study. In Kidney diseases (Basel, Switzerland), 5, 220-227. doi:10.1159/000497100. https://pubmed.ncbi.nlm.nih.gov/31768379/
7. Brown, Markus A, Dotson, Gabrielle A, Ronquist, Scott, Rajapakse, Indika, Ried, Thomas. 2021. TCF7L2 silencing results in altered gene expression patterns accompanied by local genomic reorganization. In Neoplasia (New York, N.Y.), 23, 257-269. doi:10.1016/j.neo.2020.12.010. https://pubmed.ncbi.nlm.nih.gov/33422939/
8. Ozkan Kucuk, Nazlı Ezgi, Horozoglu, Cem, Timirci Kahraman, Ozlem, Sabitaliyevich, Uteuliyev Yerzhan, Yaylim, Ilhan. 2019. Gene variants of TCF7L2 are histopathologically important in colorectal cancers but do not have direct association with MYC expression. In Cellular and molecular biology (Noisy-le-Grand, France), 65, 1-6. doi:. https://pubmed.ncbi.nlm.nih.gov/32133972/
9. Wang, Jinjin, Zhang, Jianfeng, Li, Linlin, You, Haifei, Hu, Dongsheng. 2013. Association of rs12255372 in the TCF7L2 gene with type 2 diabetes mellitus: a meta-analysis. In Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas, 46, 382-93. doi:. https://pubmed.ncbi.nlm.nih.gov/23579632/