Association between MFN2 gene polymorphisms and the risk and prognosis of acute liver failure: a case-control study in a Chinese population

This study aimed to determine the role of mitofusin 2 (MFN2) gene polymorphisms in the risk and prognosis of acute liver failure (ALF). A total of 298 blood samples were collected from 138 ALF patients (case group) and 160 healthy participants (control group). Coagulation function, glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), total bilirubin (TB), blood ammonia and lactic acid (LA) were measured. The predictive evaluation of MFN2 gene polymorphisms in the risk and prognosis of ALF patients was estimated using Kaplan-Meier survival analysis, haplotype analysis, binary logistic regression analysis and Cox regression analysis. Higher levels of GPT, GOT, TB, blood ammonia and LA were observed in ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 than in those with the CC genotype of these two SNPs. The GTACAGC and GTGTGGC haplotypes were a protective factor and a risk factor for ALF, respectively. Blood ammonia and LA levels were independent risk factors and the CC genotype of rs873457 and the CC genotype of rs4846085 were protective factors for ALF. ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 had a lower survival rate than those with other genotypes of these two SNPs. The rs4846085 and rs873457 polymorphisms were both independent factors affecting the prognosis of ALF patients. MFN2 gene polymorphisms (rs873457, rs2336384, rs1474868, rs4846085 and rs2236055) may be associated with ALF and the rs873457 and rs4846085 polymorphisms are correlated with the risk and prognosis of ALF.

本研究旨在探讨线粒体融合蛋白2（mitofusin 2, MFN2）基因多态性在急性肝衰竭（acute liver failure, ALF）的发病风险与预后中的作用。本研究共收集298份血液样本，涉及138例ALF患者（病例组）与160名健康受试者（对照组）。检测指标涵盖凝血功能、谷丙转氨酶（glutamic pyruvic transaminase, GPT）、谷草转氨酶（glutamic oxaloacetic transaminase, GOT）、总胆红素（total bilirubin, TB）、血氨及乳酸（lactic acid, LA）。本研究采用Kaplan-Meier生存分析、单倍型分析、二元logistic回归分析及Cox回归分析，评估MFN2基因多态性对ALF患者发病风险与预后的预测效能。结果显示，携带rs873457位点GG基因型或rs4846085位点TT基因型的ALF患者，其GPT、GOT、TB、血氨及LA水平均显著高于携带对应单核苷酸多态性（single nucleotide polymorphism, SNP）位点CC基因型的患者。单倍型GTACAGC与GTGTGGC分别为ALF的保护因素与危险因素。血氨与LA水平为ALF的独立危险因素，而rs873457位点CC基因型与rs4846085位点CC基因型为ALF的保护因素。携带rs873457位点GG基因型或rs4846085位点TT基因型的ALF患者，其生存率低于携带这两个位点其他基因型的患者。rs4846085与rs873457多态性均为影响ALF患者预后的独立因素。MFN2基因多态性（rs873457、rs2336384、rs1474868、rs4846085及rs2236055）可能与ALF发病相关，且rs873457与rs4846085多态性与ALF的发病风险及预后密切相关。