Hao Yangmin, Zhang Tao, Tuerxunmaimaiti Shaliyan, Tian Ye, Wang Xinyu, Li Zhiming, Zhao Liang, Bai Lei, Chen Qu, Li Cheng, Abulitipu Ayiguzhali, Wang Rui, Jiang Sheng, Du Guoli
State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, People's Republic of China.
Department of Endocrinology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People's Republic of China.
Int J Gen Med. 2025 Jun 3;18:2807-2821. doi: 10.2147/IJGM.S520326. eCollection 2025.
Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent in Xinjiang, with genetic factors influencing its pathogenesis. Keratin 23 (KRT23), a liver-enriched protein linked to metabolic regulation, remains understudied in MAFLD genetics.
To investigate associations between KRT23 gene polymorphisms, expression, and MAFLD in Xinjiang.
This study enrolled 1,795 MAFLD patients diagnosed via ultrasonography and metabolic criteria. KRT23 polymorphisms (rs72826004, rs2269859) were analyzed. GEO database screening identified MAFLD-related genes. KRT23 expression was assessed in human serum/liver tissues (ELISA, Western blot, qRT‒PCR, IHC) and murine models (high-fat diet-induced MAFLD and db/db mice).
Enrichment analysis identified 10 key MAFLD-associated genes, including KRT23. The rs72826004 TT genotype increased MAFLD risk (OR: 2.156, P=0.007), while rs2269859 TT conferred protection (OR: 0.306, P=0.002). MAFLD patients exhibited elevated KRT23 protein/mRNA levels in serum and liver versus controls. Murine models confirmed higher KRT23 expression in MAFLD and db/db mice compared to wild-type.
KRT23 gene polymorphism was associated with the occurrence of MAFLD. The rs72826004 loci TT genotype may be a risk factor for MAFLD, whereas the rs2269859 loci TT genotype may be a protective factor against MAFLD. Higher KRT23 expression (protein and mRNA) is related to MAFLD. KRT23 is a potential target for the treatment of MAFLD.
代谢功能障碍相关脂肪性肝病（MAFLD）在新疆地区高度流行，遗传因素影响其发病机制。角蛋白23（KRT23）是一种与代谢调节相关的肝脏富集蛋白，在MAFLD遗传学方面的研究仍较少。
探讨新疆地区KRT23基因多态性、表达与MAFLD之间的关联。
本研究纳入了1795例经超声检查和代谢标准确诊的MAFLD患者。分析KRT23基因多态性（rs72826004、rs2269859）。通过GEO数据库筛选确定MAFLD相关基因。采用酶联免疫吸附测定（ELISA）、蛋白质免疫印迹法、实时荧光定量聚合酶链反应（qRT-PCR）、免疫组化法评估人血清/肝组织中KRT23的表达，并在小鼠模型（高脂饮食诱导的MAFLD和db/db小鼠）中进行评估。
富集分析确定了10个与MAFLD相关的关键基因，包括KRT23。rs72826004位点的TT基因型增加了MAFLD风险（比值比：2.156，P=0.007），而rs2269859位点的TT基因型具有保护作用（比值比：0.306，P=0.002）。与对照组相比，MAFLD患者血清和肝脏中的KRT23蛋白/信使核糖核酸（mRNA）水平升高。小鼠模型证实，与野生型相比，MAFLD小鼠和db/db小鼠中KRT23的表达更高。
KRT23基因多态性与MAFLD的发生有关。rs72826004位点的TT基因型可能是MAFLD的危险因素，而rs2269859位点的TT基因型可能是预防MAFLD的保护因素。较高的KRT23表达（蛋白质和mRNA）与MAFLD相关。KRT23是治疗MAFLD的潜在靶点。
