Scnn1a,也称为钠通道上皮亚基α(ENaC α亚基),是一种编码上皮钠通道(ENaC)α亚基的基因。ENaC是一种非电压门控的钠离子通道,主要在肾脏、肺和结肠等上皮组织中表达。ENaC的功能是调节钠离子在细胞内的浓度,从而影响细胞内外的渗透压和水的平衡。Scnn1a基因的表达和功能异常与多种疾病的发生和发展密切相关,包括肿瘤、遗传性疾病和呼吸系统疾病等。
Scnn1a基因在卵巢癌中的表达与患者的预后和免疫细胞浸润相关。研究表明,与正常组织相比,Scnn1a在卵巢癌组织中高表达,并且Scnn1a的表达水平与卵巢癌患者的预后呈负相关,即Scnn1a高表达与较差的预后相关[1]。此外,Scnn1a的高表达还与免疫细胞浸润相关,这表明Scnn1a可能参与调节肿瘤免疫微环境。
Scnn1a基因突变导致的遗传性疾病包括假性醛固酮减少症1型(PHA1)。PHA1是一种罕见的遗传性疾病,表现为对醛固酮的周围抵抗,导致新生儿盐丢失综合征、低钠血症、低氯血症、高钾血症、代谢性酸中毒和醛固酮水平升高。Scnn1a基因突变导致ENaC功能异常,进而影响钠离子在肾脏和结肠等上皮组织中的转运,导致电解质平衡紊乱[2,3,7,8]。
Scnn1a基因突变还与新生儿呼吸窘迫综合征(RDS)的发生相关。RDS是一种严重的呼吸系统疾病,主要发生在早产儿和足月儿中。研究表明,Scnn1a基因的单核苷酸多态性(SNPs)与RDS的发生相关,特别是在足月儿中[6]。
Scnn1a基因的表达还与其他疾病的发生和发展相关。例如,Scnn1a基因突变导致的Liddle综合征是一种常染色体显性遗传疾病,表现为高血压、低钾血症和代谢性碱中毒。研究表明,Scnn1a基因突变导致ENaC功能异常,进而影响钠离子在肾脏中的转运,导致电解质平衡紊乱[4]。
Scnn1a基因的表达还与肿瘤的发生和发展相关。研究表明,Scnn1a基因在胰腺癌中的表达与患者的预后相关,Scnn1a的高表达与较差的预后相关[5]。
综上所述,Scnn1a基因在多种疾病的发生和发展中发挥重要作用,包括肿瘤、遗传性疾病和呼吸系统疾病等。Scnn1a基因的表达和功能异常与电解质平衡紊乱、免疫细胞浸润和肿瘤的发生和发展相关。Scnn1a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. Lou, Jiayan, Wei, Lingjia, Wang, He. 2022. SCNN1A Overexpression Correlates with Poor Prognosis and Immune Infiltrates in Ovarian Cancer. In International journal of general medicine, 15, 1743-1763. doi:10.2147/IJGM.S351976. https://pubmed.ncbi.nlm.nih.gov/35221714/
2. Serra, Gregorio, Antona, Vincenzo, D'Alessandro, Maria Michela, Verde, Vincenzo, Corsello, Giovanni. 2021. Novel SCNN1A gene splicing-site mutation causing autosomal recessive pseudohypoaldosteronism type 1 (PHA1) in two Italian patients belonging to the same small town. In Italian journal of pediatrics, 47, 138. doi:10.1186/s13052-021-01080-x. https://pubmed.ncbi.nlm.nih.gov/34134742/
3. Efthymiadou, Alexandra, Gautschi, Ivan, van Bemmelen, Miguel Xavier, Schild, Laurent, Chrysis, Dionisios. 2023. A mild and transient form of autosomal recessive pseudohypoaldosteronism type 1 caused by a novel mutation in the SCNN1A gene. In American journal of physiology. Endocrinology and metabolism, 325, E1-E9. doi:10.1152/ajpendo.00332.2022. https://pubmed.ncbi.nlm.nih.gov/37134141/
4. Tian, Jiajia, Xiang, Fei, Wang, Liandi, Ma, Li, Fang, Chuwen. 2024. Liddle Syndrome with a SCNN1A Mutation: A Case Report and Literature Review. In Kidney & blood pressure research, 49, 831-838. doi:10.1159/000540522. https://pubmed.ncbi.nlm.nih.gov/39236685/
5. Chang, Jinhai, Hu, Xuguang, Nan, Jinniang, Zhang, Xianghua, Jin, Xintian. 2021. HOXD9‑induced SCNN1A upregulation promotes pancreatic cancer cell proliferation, migration and predicts prognosis by regulating epithelial‑mesenchymal transformation. In Molecular medicine reports, 24, . doi:10.3892/mmr.2021.12459. https://pubmed.ncbi.nlm.nih.gov/34558641/
6. Li, Wang, Long, Chen, Renjun, Li, Juan, Ma, Yuan, Shi. 2015. Association of SCNN1A Single Nucleotide Polymorphisms with neonatal respiratory distress syndrome. In Scientific reports, 5, 17317. doi:10.1038/srep17317. https://pubmed.ncbi.nlm.nih.gov/26611714/
7. Alquraishi, Ali, Alshahrany, Abdullah, Alasmari, Badriah G, Hommadi, Ashwaq, Alomari, Mohammed. 2024. Pseudohypoaldosteronism Type 1b in a Saudi Female Infant Due to Homozygous Variant Gene Mutation in SCNN1A: A Case Report. In Cureus, 16, e67165. doi:10.7759/cureus.67165. https://pubmed.ncbi.nlm.nih.gov/39295704/
8. Saffari, Fatemeh, Bahadoran, Ensiyeh, Homaei, Ali, Moghbelinejad, Sahar. 2024. Novel homozygous mutation in SCNN1A gene in an Iranian boy with PHA1B. In Journal of pediatric endocrinology & metabolism : JPEM, 37, 745-749. doi:10.1515/jpem-2023-0505. https://pubmed.ncbi.nlm.nih.gov/38963175/