摘要
目的探讨CXC趋化因子配体10(C-H-C motif chemokine ligand 10,CXCL10)基因rs56061981单核苷酸多态性与乙型肝炎病毒(hepatitis B virus,HBV)相关慢加急性肝衰竭(hepatitis B virus related acute-on-chronic liver failure,HBV-ACLF)发病风险及病情严重程度的关系。方法收集86例HBV-ACLF和42例慢性乙型肝炎(chronic hepatitis B,CHB)患者入院时的血液标本。常规方法检测患者血清丙氨酸转氨酶(alanine transferase,ALT)、总胆红素(total bilirubin,TBil)、国际标准化比值(international standard ratio,INR)、肌酐(creatinine,Cr)、白蛋白(albumin,ALB)和胆碱酯酶(cholinesterase,CHE),计算终末期肝病模型(model for end-stage liver disease,MELD)评分,荧光定量PCR方法检测患者外周血单个核细胞CXCL10 mRNA水平,DNA测序法检测CXCL10基因rs56061981位点基因型。卡方检验比较ACLF和CHB组的基因型和等位基因型频率的差异。按是否携带T等位基因分组,t检验比较两组ALT、TBil、INR、MELD、ALB、CHE及CXCL10 mRNA水平的差异。结果CHB组和HBV-ACLF组比较,性别、年龄、酗酒史、吸烟史、HBV基因型、HBeAg状态和HBV-DNA水平等差异无统计学意义(P>0.05)。ACLF组CXCL10基因rs56061981位点CT+TT基因型频率和T等位基因频率均明显高于CHB组(χ^(2)=4.83,P=0.03和χ^(2)=4.95,P=0.03),有显著性差异。基因型CT+TT是CHB进展成HBV-ACLF的危险因素(OR=2.897,95%CI:1.09~7.68);等位基因T是CHB进展成HBV-ACLF的危险因素(OR=2.746,95%CI:1.10~6.89)。携带T等位基因的ACLF个体血浆INR值和MELD评分明显高于携带C等位基因的个体(t=2.63,P=0.013和t=2.7,P=0.011),有显著性差异。ALB和CHE明显低于携带C等位基因的个体(t=2.67,P=0.01和t=3.545,P=0.001),有显著性差异。而两组间血清TBiL和ALT差异无统计学意义。结论CXCL10基因rs56061981单核苷酸多态性与HBV-ACLF易感性及严重程度存在显著关联。等位基因T可能是HBV-ACLF的易感基因,可以作为患者病情严重程度的预测指标之一。
To investigate the relationship between the rs56061981 polymorphism of chemokine(C-X-C motif)ligand 10(CXCL10)gene and the risk and severity of HBV-related acute on chronic liver failure(HBV-ACLF).Methods Whole blood and serum samples were collected from 86 patients with HBV-ACLF and 42 patients with chronic hepatitis B(CHB).Serum alanine aminotransferase(ALT),total bilirubin(TBil),creatinine(Cr),albumin(ALB)cholinesterase(CHE)and international standardized ratio(INR)were detected by routine method.The CXCL10 mRNA level of peripheral blood mononuclear cells was detected by fluorescence quantitative PCR.The genotype and allele of rs56061981 were detected by direct DNA sequencing.The genotype and allele frequencies between the ACLF and CHB groups were compared.The levels of ALT,TBil,INR,ALB,CHE,model for end-stage liver disease(MELD)and CXCL10 mRNA were compared between the two groups according to whether the T allele was carried.Results There was no significant difference in sex,age,alcohol history,smoking history,HBV genotype,HBeAg status and HBV-DNA level between CHB group and HBV-ACLF group(P>0.05).The frequency of CT+TT genotype and the frequency of T allele at the rs56061981 locus of the CXCL10 gene in group ACLF were significantly higher than that in the CHB group(χ^(2)=4.83,P=0.03 andχ^(2)=4.95,P=0.03).The difference is significant Genotype CT+TT is a risk factor for CHB to develop into HBV-ACLF(OR=2.897,95%CI:1.09~7.68).Allele T is a risk factor for CHB to develop into HBV-ACLF(OR=2.746,95%CI:1.10~6.89).The plasma INR and MELD scores of ACLF individuals carrying T alleles were significantly higher than those carrying C alleles(t=2.63,P=0.013 and t=2.7,P=0.011).The difference is significant.Albumin(ALB)and cholinesterase(CHE)was significantly lower than those carrying C alleles(t=2.67,P=0.01 and t=3.545,P=0.001).The difference is significant.But there was no significant difference in serum TBL and ALT between the two groups.Conclusions The polymorphism of CXCL10 gene rs56061981 is significantly correlated with the susceptibility and severity of ACLF.Allele T may be a susceptible gene of ACLF,and it can also be used as a predictor of the severity of the disease.
作者
黄少军
付文荣
汪晶晶
程正江
陈秀记
王晓霖
Huang Shaojun;Fu Wenrong;Wang Jingjing;Cheng Zhengjiang;Chen Xiuji;Wang Xiaolin(Department of Medical Laboratory,Xiangyang Central Hospital Affiliated to Hubei University of Arts and Science,Xiangyang 441021,China;Department of Pathology,Xiangyang Central Hospital Affiliated to Hubei University of Arts and Science,Xiangyang 441021,China;Department of Gastroenterology,Xiangyang Central Hospital Affiliated to Hubei University of Arts and Science,Xiangyang 441021,China)
出处
《中华实验和临床病毒学杂志》
CAS
CSCD
2022年第1期97-102,共6页
Chinese Journal of Experimental and Clinical Virology
基金
湖北省自然科学基金(2013CFB385)
湖北省襄阳市研究与开发计划(2017-10-34)。
