摘要
目的：探讨IL-1β、IL-1ra血清水平及白细胞介素-1B（ IL-1B）和白细胞介素-1RN（ IL-1RN）基因多态性与HCV相关肝病发生发展的关系。方法以酶联免疫吸附试验（ ELISA）测定IL-1β、IL-1ra血清水平；基因芯片技术检测310例HCV肝病和324例不相关联的健康对照人群的IL-1B-31 C/T、IL-1B-511C/T单核苷酸多态性（SNP）；琼脂糖凝胶电泳检测IL-1RN内含子2（intron 2）基因多态性（ VNTR）。聚合酶链反应-限制性片段长度多态性（ PCR-RFLP）随机分析部分样本验证基因芯片分型结果；HCV基因分型采用直接测序法；Lightcycler 特异性荧光探针PCR检测HCV RNA载量；血清丙氨酸氨基转移酶（ alanine aminotransferase ，ALT）使用ROCHE cobas 8000全自动生化分析仪检测。结果（1）病例组IL-1β血清水平（22.6±7.3） pg/ml显著高于对照组（13.7±4.2） pg/ml（ P＜0.01）；IL-1ra血清水平（286.30±55.10） pg/ml显著高于对照组（185.55±48.32） pg/ml（P＜0.01）。（2）在病例组、轻中型肝炎、重型肝炎、肝硬化合并肝癌组、1b型组及2a型组，IL-1B-511T等位基因携带者血清IL-1β水平均显著高于其相应CC纯和子及对照组（ P＜0.05），且HCV感染各组-511 T携带者IL-1ra/IL-1β比值显著低于对照组（P＜0.05）；IL-1B-511T携带者在1b型组的IL-1β水平较2a型组显著增高（P＜0.05）；IL-1B-511T携带者IL-1ra血清水平显著高于相应对照组（P＜0.05）；IL-1B-511CC携带者血清IL-1β水平在各组别间差异无统计学意义（P＞0.05）。（3）病例组IL-1B-511TT基因型频率显著高于对照组（ P＜0.05，OR＝1.55，95％CI＝1.10～2.18），两组间T等位基因频率差异有统计学意义（P＜0.05，OR＝1.31，95％CI＝1.05～1.63）。 IL-1RN VNTR二组间差异无统计学意义（P＞0.05）。（4）IL-1B-511C/T SNP基因型频率在不同转归类型中差异有统计学意义（ P＜0.005）。与相应的CT＋CC基因型比较，不同�
Objective To study the characteristics of IL-1B-31/-511 single nucleotide polymor-phisms （SNPs） and the variable number tandem repeat （VNTR） in intron 2 of the IL-1ra gene （IL-1RN） in patients with HCV-related liver diseases .Methods The concentration of IL-1βand IL-1ra in serum sam-ples was measured by ELISA assay .The SNPs of IL-1B gene （-31C/T,-511C/T） from 310 cases with HCV infection and 324 unrelated healthy controls were determined by using gene chip analysis , and the results for some randomly selected specimens were compared with those by using polymerase chain reaction -restriction fragment length polymorphism （ PCR-RFLP） assay.The VNTR polymorphism of IL-1RN intron 2 was ana-lyzed by PCR-RFLP assay.The serum level of alanine aminotransferase （ALT）, an indicator of hepatocellu-lar injury, was detected by ROCHE cobas 8000 analyzer.HCV replication was measured by using specific fluorescence PCR .The genotypes of HCV were determined by direct nucleotide sequencing test .Results Compared with control group, the serum level of both IL-1β[（22.6 ±7.3） vs （13.7 ±4.2）] pg/ml and IL-1ra [（286.30 ±55.10） vs （185.55 ±48.32）] pg/ml were significantly increased in patients with HCV infection （ P〈0.01 ） .There were two predominant genotypes identified among 310 patients including HCV 1b （75.5%） and HCV 2a （22.3%）.The serum level of IL-1βand IL-1ra in IL-1B-511T carriers from four groups including case group , mild and moderate Hepatitis C group , severe Hepatitis C , and cirrhosis and hepatocellular carcinoma （HCC） group were significantly higher than those from IL-1B-511CC carriers and control group （P〈0.05）.The ratio of IL-1ra to IL-1βin all IL-1B-511T carriers with HCV infection were lower than those from healthy controls （P〈0.05）.IL-1B-511T carriers with HCV genotype 1b infec-tion showed a higher serum level of IL-1βas compared with those with HCV genotype 1a infection （ P〈0.05）.Compared with control group, they also showed an inc
出处
《中华微生物学和免疫学杂志》
CAS
CSCD
北大核心
2014年第3期186-193,共8页
Chinese Journal of Microbiology and Immunology
基金
山东省教育厅立项课题（JIDLF71）
