目的探讨白介素-18(IL-18)基因启动子区-137G/C(rs187238)和-607C/A(rs1946518)单核苷酸多态性(SNP)与慢性乙型病毒性肝炎(乙肝)病毒感染之间的关系。方法选取2007年3月至2010年10月期间就诊于桂林市疾病预防控制中心和桂林医学院附属医院的慢性乙肝患者作为病例组,共264例;另外选取同期在上述两个单位进行体检,均无慢性乙肝病史的健康者作为对照组,共300例。采用序列特异性引物一聚合酶链反应技术(SSP—PCR),检测上述二组研究对象IL-18基因启动子-137G/C(rs187238)、-607C/A(rsl946518)单核苷酸多态性位点基因型,分析病例组和对照组基因型和等位基因频率分布。结果病例组IL-18基因多态性位点rs1946518的基因型和等位基因的频率与对照组相比差异无统计学意义(P〉0.05)。但是,病例组IL-18基因SNP位点rs187238G等位基因的频率高于对照组(OR=1.353,95%CI:1.009-1.815,P=0.043)。携带rs187238GG基因型的患者发生慢性乙肝的风险较高(OR=1.629,95%CI:1.152—2.305,P=0.006)。分层分析发现,rs187238位点上Gc基因型和C等位基因的频率与慢性乙肝的关联在乙肝e抗原(ttBeAg)阳性组的患者中更加显著(P=0.022,P=0.011)。结论IL-18基因启动子区-137G/C(rs187238)多态性与慢性乙肝易感性具有相关性,而且,rs187238位点上GC基因型和C等位基因的频率与HBeAg阳性的慢性乙肝患者具有相关性。
Objective To investigate the relationship between the single nucleotide polymorphisms (SNP) - 137G/C ( rs187238 ) and - 607C/A ( rs1946518 ) in the promoter region of Interleukin - 18 ( IL - 18 ) gene and chronic hepatitis B virus infection. Methods Case-control study was conducted among 264 chronic hepatitis B cases and 300 healthy controls seeking medical care in Guilin Municipal Center for Disease Control and Prevention and Affiliated Hospital of Guilin Medical College from March 2007 to October 2010. The SNP at the position of IL - 18 gene promoter - 137G/C (rs187238) and -607C/A (rs1946518) were detected by sequence specific primer-polymerase chain reaction (SSP- PCR). The genotype and allele frequencies were analyzed for both case group and control group. Results At rs1946518, the difference in the genotype and allele frequencies of IL - 18 gene polymorphism between case group and control group was not significant (P 〉 0. 05 ). but, at rs187238, G allele frequency was significantly higher ( OR = 1. 353, 95% CI: I. 009 - 1. 815, P = 0. 043 ) in case group. Patients who carried rs187238 GG genotype had higher risk of suffering from chronic hepatitis B ( OR = 1. 629,95% CI: 1. 152 - 2. 305 ,P = 0. 006). Stratified analysis showed that rs187238 GC genotypes and C allele frequency were significantly associated in chronic hepatitis B patients who were HBeAg positive ( P = 0. 022, P = 0. 011, respectively ). Conclusion IL-18 gene promoter-137G/C (rs187238) polymorphism is correlated with chronic hepatitis B, and rs187238 GC genotypes and C allele frequency are respectively associated with chronic hepatitis B patients who are HBeAg positive.