摘要
目的研究一种高加索人群丙型肝炎肝硬化风险评分模型（cirrhosis risk score，CRS）相关基因的多态性与中国人群乙型肝炎肝硬化的关系，评估该模型在乙型肝炎肝硬化中的应用价值。方法用基质辅助激光解析电离飞行时间质谱法检测相关的11个单核苷酸多态性位点，研究人群包括肝硬化组患者和对照组无肝硬化表现者，分析各位点与肝硬化的关系，比较肝硬化组和对照组CRS值的差异。用x^2检验检测哈维平衡验证样本的群体代表性。两组计量资料的比较用f检验或Wilcoxon秩和检验。单个单核苷酸多态性基因型等分类数据与肝硬化发生的关系用Pearson X^2检验，差异有统计学意义的单核苷酸多态性位点进一步用Logistic回归分析判断在显性模型、隐性模型和加性模型下基因型与肝硬化发生的关系，计算比值比及95％可信区间，比值比经性别和年龄校正。结果鸟氨酸脱羧酶抗酶抑制因子1基因的rs2679757位点与肝硬化的发生相关（x^2=6．79，P〈0．05），与AA纯合子相比，携带危险等位基因G的GG＋AG基因型显著增加肝硬化的发生风险，比值比为1．63，95％可信区间为1．13～2．35。位于Toll样受体4基因的rs4986791位点和鸟氨酸脱羧酶抗酶抑制因子1基因的rs62522600位点在中国人群中无多态性基因型。其他研究位点与肝硬化的发生无相关性（JD〉0．05）。肝硬化组和对照组的CRS中位数分别为0．57和0．62，两组比较，差异无统计学意义（P〉0．05）。结论鸟氨酸脱羧酶抗酶抑制因子1多态性rs2679757与乙型肝炎肝硬化的发生相关。高加索人群CRS模型相关的两个多态性位点在中国人群中缺乏多态性，该CRS对评估有无乙型肝炎肝硬化的发生无明显价值，其他多态性位点仍需进一步临床验证。
Objective A cirrhosis risk score （CRS） comprised of single nucleotide polymorphisms （SNPs） in seven genes that predicts the risk of cirrhosis in Caucasian hepatitis C has been reported. The present study was to evaluate the association of 11 separate but related SNPs and the CRS with cirrhosis risk in Chinese hepatitis B patients. Methods A total of 563 Chinese subjects with persistent HBV infection （349 with evident liver cirrhosis and 214 without cirrhosis clinically or pathologically） were studied. The candidate SNPs were detected with a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF MS） method. The allele frequency and genotype distribution of each polymorphism as well as the CRS value within the cirrhosis and non-cirrhosis subjects were compared. Results The rs2679757 polymorphism of the antizyme inhibitor 1 （AZIN1） gene was associated with the risk of cirrhosis （ x^2 = 6.79, P = 0.03, odds ratio for GG＋AG versus AA = 1.63, 95% confidence interval = 1.13-2.35）. A gene variant （rs886277） in the transient receptor potential cation channel subfamily M, member 5 gene （TRPM5） was associated with liver cirrhosis, but did not reach statistical significance （ x^2 = 5.77, P = 0.06）. Two SNPs （rs4986791, rs62522600） are not polymorphic in Chinese. Genotype frequencies of other SNPs were not different between the cirrhosis and non-cirrhosis groups. The overall CRS values were not different between the cirrhotic and non-cirrhotic groups （median value 0.57 versus 0.62, Z = -1.05, P = 0.29）. Conclusions SNP rs2679757 in the AZIN1 gene is associated with the risk of HBV-related liver cirrhosis in Chinese. The CRS for Caucasian population has limited applicability for predicting liver cirrhosis in Chinese hepatitis B patients. SNPs associated with cirrhosis prognosis in hepatitis B patients and liver diseases with other etiologies warrant further clinical validation.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2011年第3期169-173,共5页
Chinese Journal of Hepatology
基金
上海市浦江人才计划基金（09PJ1402600）
中国肝炎防治基金会王宝恩肝纤维化研究基金（20090001）
关键词
肝硬化
多态性
单核苷酸
鸟氨酸脱羧酶
Liver cirrhosis
Polymorphism, single nucleotide
Ornithine decarboxylase
