Pineda-Tenor Daniel, Gómez-Moreno Ana Zaida, Sánchez-Ruano Juan José, Artaza-Varasa Tomas, Virseda-Berdices Ana, Fernández-Rodríguez Amanda, Mendoza Pedro Molina, Jiménez-Sousa María Ángeles, Resino Salvador
Servicio de Laboratorio Clínico, Hospital de Antequera, Málaga, Spain.
Servicio de Digestivo, Hospital Virgen de la Salud, Toledo, Spain.
Front Med (Lausanne). 2020 Nov 13;7:582666. doi: 10.3389/fmed.2020.582666. eCollection 2020.
The (methylenetetrahydrofolate reductase) rs1801133 polymorphism leads to higher circulating levels of homocysteine, which is related to several liver diseases. We aimed to evaluate the relationship between rs1801133 polymorphism and liver fibrosis progression in HCV-infected patients. We conducted a preliminary retrospective cohort study in 208 non-cirrhotic HCV-infected patients. These subjects had at least two liver stiffness measurements (LSM), which were assessed using transient elastography, and no patient had cirrhosis at baseline. We analyzed the association between rs1801133 and outcome variables using Generalized Linear Models. HCV-infected patients were 47 years old, around 54% were males, a low frequency of high alcohol intake (13.5%) or prior use of intravenous drugs (10.1%). A total of 26 patients developed cirrhosis (LSM1 ≥ 12.5) during a median follow-up of 46.6 months. The presence of the rs1801133 C allele showed an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.90; 95%CI = 0.83-0.98; = 0.020) and the cirrhosis progression (adjusted OR = 0.43; 95%CI = 0.19-0.95; = 0.038). Besides, rs1801133 CT/CC genotype had an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.80; 95%CI = 0.68-0.95; = 0.009) and the cirrhosis progression (adjusted OR= 0.21; 95%CI = 0.06-0.74; = 0.015). rs1801133 C allele carriers presented a diminished risk of liver fibrosis progression and development of cirrhosis than rs1801133 T allele carriers. This statement supports the hypothesis that rs1801133 polymorphism appears to play a crucial role in chronic hepatitis C immunopathogenesis.
亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase，MTHFR）基因rs1801133多态性会导致循环中的同型半胱氨酸水平升高，而这与多种肝脏疾病相关。我们旨在评估rs1801133多态性与丙型肝炎病毒（HCV）感染患者肝纤维化进展之间的关系。我们对208例非肝硬化HCV感染患者进行了一项初步回顾性队列研究。这些受试者至少进行了两次肝脏硬度测量（LSM），采用瞬时弹性成像技术进行评估，且在基线时无患者患有肝硬化。我们使用广义线性模型分析rs1801133与结局变量之间的关联。HCV感染患者的年龄为47岁，约54%为男性，高酒精摄入量的频率较低（13.5%）或既往使用过静脉注射药物的频率较低（10.1%）。在中位随访46.6个月期间，共有26例患者发展为肝硬化（LSM1≥12.5）。rs1801133 C等位基因的存在与LSM2/LSM1比值呈负相关（校正后AMR = 0.90；95%CI = 0.83 - 0.98；P = 0.020）以及与肝硬化进展呈负相关（校正后OR = 0.43；95%CI = 0.19 - 0.95；P = 0.038）。此外，rs1801133 CT/CC基因型与LSM2/LSM1比值呈负相关（校正后AMR = 0.80；95%CI = 0.68 - 0.95；P = 0.009）以及与肝硬化进展呈负相关（校正后OR = 0.21；95%CI = 0.06 - 0.74；P = 0.015）。与rs1801133 T等位基因携带者相比，rs1801133 C等位基因携带者肝纤维化进展和肝硬化发生的风险降低。这一结果支持了rs1801133多态性似乎在慢性丙型肝炎免疫发病机制中起关键作用这一假说。
