汉族人白细胞介素-18基因启动子多态性与慢性乙型肝炎的相关性研究

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一聚合酶链反应技术，检测231例慢性乙型肝炎患者和300名正常人儿．馏基因启动子-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Y0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（X^2=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儿．馏基因启动子多态性与乙型肝炎病毒（hepatitis Bvirus，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（Y2=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。

Relationship of interleukin-18 gene promoter polymorphisms with chronic hepatitis B in Chinese Han population

OBJECTIVE: To investigate the polymorphisms of interleukin-18(IL-18) gene promoters, and to disclose whether such polymorphisms are associated with susceptibility to chronic hepatitis B in Chinese Han population. METHODS: Using polymerase chain reaction with sequence specific primers method, the authors detected the single nucleotide polymorphisms of the promoter region of IL-18 gene at position -607C/A and -137G/C in 231 patients with chronic hepatitis B and 300 normal controls. RESULTS: The frequency of CC genotype in IL-18 gene promoter region at position -607 was 0.22(66/300) in normal controls and 0.27(62/231) in patients. The frequency of CA genotype was 0.53(160/300) in normal controls and 0.50(116/231) in patients. The frequency of AA genotype was 0.25(74/300) in normal controls and 0.23(53/231) in patients. The frequencies of -137GG, GC and CC genotype were 0.67, 0.30 and 0.03 in normal controls respectively; whereas in chronic hepatitis B patients the frequencies were 0.79, 0.19 and 0.02. The genotype frequency of -137GG in chronic hepatitis B groups was significantly higher than that in normal controls(chi2: 8.55, P=0.003), but the frequencies of -607C/-137C and -607A/-137C haplotypes in chronic hepatitis B groups were significantly lower than those in normal controls. The association between genotype of IL-18 promoter region polymorphisms and hepatitis B virus(HBV) copies showed that the frequency of -607AA genotype in high HBV-DNA copies groups was lower than that in low HBV-DNA copies groups(chi2: 6.03, P=0.014). CONCLUSION: The polymorphisms of the promoter region of IL-18 gene at position -607C/A and -137G/C are correlated with chronic hepatitis B in Chinese Han population. The people with -137C allele in the promoter region of IL-18 gene may be protected against HBV infection, and the IL-18 -607AA genotype may be linked to HBV-DNA copy.