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目的探讨中国汉族人白细胞介素-18(interleukin-18,IL-18)基因启动子单核苷酸多态性及其与慢性乙型肝炎易感性之间的关系。方法应用序列特异性引物-聚合酶链反应技术,检测231例慢性乙型肝炎患者和300名正常人IL-18基因启动子-607C/A、-137G/C单核苷酸多态性位点基因型。结果正常对照组和慢性乙型肝炎组中,IL-18基因启动子-607C/A位点3种基因型频率分别为CC型:0.22(66/300)和0.27(62/231),CA型:0.53(160/300)和0.50(116/231),AA型:0.25(74/300)和0.23(53/231);IL-18基因启动子-137G/C位点3种基因型频率分别为GG型:0.67(202/300)和0.79(182/231),GC型:0.30(90/300)和0.19(45/231),CC型:0.03(8/300)和0.02(4/231)。经χ2检验,慢性乙型肝炎组IL-18基因启动子-137GG分布频率显著高于正常对照组(χ2=8.55,P=0.003),而-607C/-137C和-607A/-137C单倍型频率显著低于正常对照组。进一步比较慢性乙型肝炎患者IL-18基因启动子多态性与乙型肝炎病毒(hepatitisB virus,HBV)DNA复制的关系,发现高水平HBV-DNA组-607位点AA基因型分布频率明显低于低水平HBV-DNA组(χ2=6.03,P=0.014)。结论汉族人慢性乙型肝炎与IL-18基因启动子-607C/A、-137G/C单核苷酸多态性相关,其中IL-18基因启动子-137位点C等位基因可能对机体HBV感染有保护作用,而启动子-607位点AA型对感染后HBV-DNA的复制可能有抑制作用。
Objective To explore the relationship between single nucleotide polymorphisms of interleukin-18 (IL-18) gene promoter and susceptibility to chronic hepatitis B in Chinese Han population. Methods Sequence-specific primer-polymerase chain reaction (PCR) was used to detect the presence of -607C / A and -137G / C single nucleotide polymorphisms in IL-18 gene promoter in 231 patients with chronic hepatitis B and 300 normal subjects genotype. Results The frequency of IL-18 gene promoter -607C / A in the normal control group and chronic hepatitis B group was CC (0.22 (66/300) and 0.27 (62/231) respectively) : 0.53 (160/300) and 0.50 (116/231), AA type: 0.25 (74/300) and 0.23 (53/231) respectively. The genotype frequency of IL-18 gene promoter-137G / Were GG type 0.67 (202/300) and 0.79 (182/231), GC type 0.30 (90/300) and 0.19 (45/231) and CC type 0.03 (8/300) and 0.02 ). The frequency of IL-18 gene promoter-137GG in chronic hepatitis B group was significantly higher than that in the normal control group (χ2 = 8.55, P = 0.003) by χ2 test, but -607C / -137C and -607A / -137C haplotype The frequency was significantly lower than the normal control group. Further comparison of the relationship between IL-18 gene promoter polymorphism and hepatitis B virus (HBV) DNA replication in patients with chronic hepatitis B found that AA genotype distribution at -607 locus in high-level HBV-DNA group was significantly lower Low-level HBV-DNA group (χ2 = 6.03, P = 0.014). Conclusion Chronic hepatitis B is associated with single nucleotide polymorphisms of -607C / A and -137G / C in IL-18 gene promoter. The C allele of IL-18 gene promoter at position -137 may affect the body HBV infection has a protective effect, and the promoter -607 AA genotype may have an inhibitory effect on HBV-DNA replication after infection.