Ⅱ类反式激活因子启动子Ⅳ区C-1350T和G-944C多态性与乙型肝炎肝硬化易感性的关系

An analysis on the relationship between susceptibility to cirrhosis and polymorphisms at C-1350T and G-944C sites of CIITA gene promoter Ⅳ in chronic HBV carriers

目的探讨Ⅱ类反式激活因子（CIITA）启动子Ⅳ区1350和-944位点单核苷酸多态性（SNP）与乙型肝炎肝硬化易感性的关系。方法在191例慢性乙型肝炎、353例乙型肝炎肝硬化与125名无HBV感染的健康献血员人群中，应用序列特异性引物PCR技术对CIITA基因启动子Ⅳ区C1350T和G-944C位点进行基因分型研究。结果慢性乙型肝炎患者CC：37．2％、TG：42．2％、CG：18．9％，肝硬化患者CC：35．3％、TG：34．0％，CG：29．3％，肝硬化患者CC、TG单倍型频率较低，而CG单倍型频率显著升高，差异有统计学意义（CG比CC：x^2=8．274，df=1，P〈0．01；CG比TG：x2=15．027，df=1，P〈0．01）；两组患者间CC与TG单倍型频率比较，x^2=1．231，df=1，P〉0．05，差异无统计学意义。与慢性乙型肝炎患者（CC／CC：12．6％；TG／TG：18．3％；含CG的基因型：33．5％；不含CG的基因型：35．6％）相比，肝硬化人群中CC／CC（1组，19．6％）和含CG的基因型（3组，53．5％）频率显著升高，而TG／TG（2组，11．9％）和不含CG的基因型（4组，15．0％）频率显著降低（1组比2组，X2=7．176，df=1，P〈0．01；1组比4组，x^2=19．818，df=1，P〈0．01；3组比2组，x2=11．423，df=1，P〈0．01；3组比4组，x2=34．226，df=1，P〈0．01；1组比3组，x2=0．009，df=1，P〉0．05；2组比4组，x2=2．176，df=1，P〉0．05）。结论CIITA基因启动子Ⅳ区中1350和-944位点多态性与慢性HBV感染者肝硬化的易感性密切相关，携带含CG单倍型的基因型人群更容易发展为肝硬化。

Objective To investigate the relationship between the susceptibility to cirrhosis and the single nucleotide polymorphisms （SNPs） at C-1350T and G-944C loci of class Ⅱ transactivator （CIITA） gene promoter Ⅳ in chronic HBV carriers. Method C-1350T and G-944C loci of CIITA gene promoter IV were analyzed by sequence-specific primer PCR （PCR-SSP） in 544 chronic HBV carriers and 125 non-HBV infected healthy blood donors. Results Among the chronic viral hepatitis B patients, there were significantly decreased frequencies of CC and TG halotypes, and significantly increased frequency of CG halotype among patients with liver cirrhosis （CG vs. CC： x^2 = 8.274, df = 1, P 〈 0.01; CG vs. TG： x^2 = 15.027, df =1, P 〈 0.01）. There were no significant differences in the frequencies of CC and TG halotypes between chronic hepatitis B and liver cirrhosis patients （ x^2= 1.231, df =1, P 〉 0.05）. There were significantly increased frequencies of CC/CC （Group 1） genotype and genotypes contained CG halotype （Group 3）, and significantly decreased frequencies of TG/TG （Group 2） genotype and genotypes that did not contain CG halotype （Group 4） among patients with liver cirrhosis; （Group 1 vs Group 2, x^2 = 7.176, df = 1, P 〈 0.01; Groupl vs Group 4, x^2 = 19.818, df= 1, P〈 0.01; Group 3 vs Group 2, x^2 = 11.423, df= 1, P〈 0.01; Group 3 vs Group 4, x^2 = 34.226, df = 1, P 〈 0.01; Group 1 vs Group 3, x ^2 = 0.009, df = 1, P 〉 0.05; Group 2 vs Group 4, x 2 = 2.176, df = 1, P 〉 0.05）. Conclusion Polymorphisms at - 1350 and -944 loci of CIITA gene promoter IV are associated with susceptibility to liver cirrhosis in chronic HBV carriers. The chronic HBV carriers bearing CC/CC genotype or genotyp＇es containing CG halotype progess into liver cirrhosis with more probability.