Gao Qiu-ju, Liu Dian-wu, Zhang Shi-yong, Jia Min, Wu Li-hong
Department of Preventive Medicine, Bethune Military Medical College of PLA, Shijiazhuang 050081, China.
Zhonghua Liu Xing Bing Xue Za Zhi. 2010 Mar;31(3):324-8.
To explore the association between polymorphisms of interferon-gamma gene intron 1 at position +874 (IFN-gamma+874) gene and the susceptibility of HBV and/or HCV infection with different clinical outcomes.
IFN-gamma+874 gene SNP were detected in 277 subjects including 79 chronic HBV/HCV coinfections, 69 individuals only with HBV infection, 55 individuals only with HCV infection and 74 controls, by sequence specific primers-PCR (SSP-PCR). Hepatocellular injury as suggested by alanine aminotransferase (ALT) was detected by Beckman LX-20. The status of viral particles in serum was determined by RT-nPCR. The possible association of the polymorphism of IFN-gamma+874 with the susceptibility of HBV and/or HCV infection and the outcome of these infections were analyzed.
(1) IFN-gamma+874 AA frequency in individuals with chronic HBV, HCV, HBV/HCV coinfections were significant higher than that in controls (chi(2) = 16.15, P = 0.01);OR (95%CI) of IFN-gamma+874 AA in chronic infection with HBV, HCV, HBV/HCV coinfections appeared to be 2.70 (1.24 - 5.92), 3.22 (1.43 - 7.25) and 4.02 (1.88 - 8.55) compared with +874 TA. No significant differences were found among HBV, HCV, HBV/HCV coinfections (chi(2) = 1.97, P = 0.73). There were no significant association of IFN-gamma+874 A/T allele frequency with HBV and/or with HCV infection (chi(2) = 4.87, P = 0.18). (2) The clinical outcomes of mild chronic hepatitis (CH), moderate/severe CH and cirrhosis with HBV and/or HCV infection were associated with IFN-gamma+874 AA [chi(2) = 14.17, P = 0.03; OR = 3.09 (1.51 - 6.33), 3.85 (1.70 - 8.70), 3.14 (1.08 - 9.17)]. No significant relationships were found between IFN-gamma+874 A/T allele frequency and the clinical outcome of HBV/HCV infection (chi(2) = 6.07, P = 0.11). (3) There were no significant associations of IFN-gamma+874 genotype/allele frequency with HCV duplication (chi(2) = 2.36, P = 0.31). (4) There were no significant associations of IFN-gamma+874 genotype/allele frequency with abnormal ALT (chi(2) = 0.15, P = 0.93).
These results suggested that polymorphisms in the IFN-gamma+874 had some influence on chronic HCV and/or HBV infection, and on the outcome of HCV and/or HBV infections. IFN-gamma+874 AA genotype and T allele were possible risk to chronic HBV and/or HCV infections and to the outcomes of HBV and/or HCV infection. However, IFN-gamma+874 TA genotype might serve as possible protective factors to them.
探讨干扰素-γ基因内含子1第+874位（IFN-γ+874）基因多态性与乙肝病毒（HBV）和/或丙肝病毒（HCV）感染易感性及不同临床结局之间的关联。
采用序列特异性引物聚合酶链反应（SSP-PCR），对277名受试者进行IFN-γ+874基因单核苷酸多态性（SNP）检测，其中包括79例慢性HBV/HCV合并感染患者、69例仅HBV感染患者、55例仅HCV感染患者及74名对照者。通过贝克曼LX-20检测丙氨酸氨基转移酶（ALT）提示的肝细胞损伤情况。采用逆转录巢式聚合酶链反应（RT-nPCR）测定血清中病毒颗粒状态。分析IFN-γ+874基因多态性与HBV和/或HCV感染易感性及这些感染结局之间的可能关联。
（1）慢性HBV、HCV、HBV/HCV合并感染患者中IFN-γ+874 AA基因型频率显著高于对照者（χ² = 16.15，P = 0.01）；与+874 TA基因型相比，慢性HBV、HCV、HBV/HCV合并感染中IFN-γ+874 AA基因型的比值比（OR）及95%可信区间（CI）分别为2.70（1.24 - 5.92）、3.22（1.43 - 7.25）和4.02（1.88 - 8.55）。HBV、HCV、HBV/HCV合并感染组之间差异无统计学意义（χ² = 1.97，P = 0.73）。IFN-γ+874 A/T等位基因频率与HBV和/或HCV感染无显著关联（χ² = 4.87，P = 0.18）。（2）轻度慢性肝炎（CH）、中度/重度CH及肝硬化合并HBV和/或HCV感染的临床结局与IFN-γ+874 AA基因型相关[χ² = 14.17，P = 0.03；OR分别为3.09（1.51 - 6.33）、3.85（1.70 - 8.70）、3.14（1.08 - 9.17）]。IFN-γ+874 A/T等位基因频率与HBV/HCV感染临床结局无显著关联（χ² = 6.07，P = 0.11）。（3）IFN-γ+874基因型/等位基因频率与HCV复制无显著关联（χ² = 2.36，P = 0.31）。（4）IFN-γ+874基因型/等位基因频率与ALT异常无显著关联（χ² = 0.15，P = 0.93）。
这些结果表明，IFN-γ+874基因多态性对慢性HCV和/或HBV感染及其感染结局有一定影响。IFN-γ+874 AA基因型和T等位基因可能是慢性HBV和/或HCV感染及其感染结局的危险因素。然而，IFN-γ+874 TA基因型可能是其保护因素。
