白细胞介素1B及受体拮抗剂基因多态性与慢性乙型肝炎的相关性

Relationship of interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms with chronic hepatitis B

目的 探讨白细胞介素 1B(interlukin- 1B,IL - 1B)基因启动子区域 - 5 11C/ T和白细胞介素1受体拮抗剂 (receptor antagonist,RN )基因在慢性乙型肝炎及正常人群中的多态性 ,初步分析其基因型与慢性乙型肝炎的相关性。 方法 对 190例慢性乙型肝炎患者和 2 4 9名正常人 IL - 1B、 RN基因进行PCR扩增 ,其中 IL - 1B基因用 Ava 限制性内切酶对 PCR产物进行消化 ,然后经琼脂糖凝胶电泳分别对IL- 1B、RN基因多态性进行分析。 结果 IL- 1B基因在正常人和慢性乙型肝炎患者中 - 5 11C等位基因频率分别为 0 .5 0和 0 .4 8,- 5 11T等位基因频率分别为 0 .5 0和 0 .5 2。 3种基因型频率分别为 CC型 :0 .2 6(6 5 / 2 4 9)和 0 .2 4 (4 5 / 190 ) ;CT型 :0 .4 7(118/ 2 4 9)和 0 .4 9(94 / 190 ) ;TT型 :0 .2 7(6 6 / 2 4 9)和 0 .2 7(5 1/190 )。IL- 1B基因启动子 - 5 11位点 CC型慢性乙型肝炎患者乙肝病毒 DNA水平明显降低 (P<0 .0 5 )。在IL- 1RN的 5种不同组合等位基因 ,只发现 1/ 1、1/ 2、2 / 2和 1/ 4四种基因型 ,其在慢性乙型肝炎患者和正常人中的分布为 1/ 1型 :0 .88和 0 .81;1/ 2型 :0 .0 9和 0 .16 ;2 / 2型 :0 .0 1和 0 .0 1;1/ 4型 :0 .0 2和 0 .0 2。其中 IL - 1RN* 1等位基因频率在慢性乙型肝?

Objective To investigate the polymorphisms of interleukin-1B(IL-1B)promoter region -511C/T and interleukin-1 receptor antagonist( RN)gene, the relationship between the genotype of IL-1B and IL-1RN, and the susceptibility to chronic hepatitis B in Chinese population. Methods Genomic DNA was extracted from the peripheral blood of 190 patients with chronic hepatitis B and 249 normal controls and then was subjected to PCR amplification. The PCR product was digested by restriction endonuclease AvaⅠ. The product of digestion was subjected to 2% gel electrophoresis and ethidium bromide staining. Results The IL-1B -511C allele was detected in 0.50 of normal controls and 0.48 of patients, while the IL-1B -511T allele was detected in 0.50 of normal controls and 0.52 of patients. The frequency of CC genotype was 0.26(65/249)and in normal controls 0.24(45/190)in patients. The frequency of CT genotype was 0.47(118/249) in normal controls and 0.49(94/190)in patients. The frequency of TT genotype was 0.27(66/249)in normal controls and 0.27(51/190)in patients.The HBV-DNA copies in chronic hepatitis B with CC genotype were significantly decreased, compared with controls (P<0.05). Only four (1/1, 1/2, 2/2 and 1/4) of the five kinds of polymorphism of IL-1RN were found in this study. The frequencies of 1/1, 1/2, 2/2 and 1/4 were 0.88, 0.09, 0.01 and 0.02 in chronic hepatitis B patients respectively, while in controls were 0.81, 0.16, 0.01 and 0.02. The IL-1 RN*1 allele was detected in 0.94 of chronic hepatitis B patients and in 0.90 of controls, while the IL-1RN*2 allele was detected in 0.05 of patients and in 0.09 of normal controls. The frequencies of 1/2 genotype and IL-1RN*2 allele were lower in chronic hepatitis B than in controls (P<0.05). Conclusion The polymorphisms of the promoter region -511C/T of IL-1B gene and IL-1RN intron 2 gene are associated with the development of chronic hepatitis B. The people with IL-1RN*2 allele may be protected against HBV infection, and the IL-1B -511 CC genotype may be linked to HBV-DNA copy.