The gene polymorphism of IL-1B and IL-1RN intron 2 and their relationships with the progression of HCV-related liver diseases
10.3760/cma.j.issn.0254-5101.2014.03.004
- VernacularTitle:IL-1B及IL-1RN内含子2基因多态性在HCV相关肝病中的分布特征
- Author:
Peixiang XING
;
Chuanxin WANG
;
Lishui WANG
;
Hongchun WANG
;
Quantai XING
- Publication Type:Journal Article
- Keywords:
HCV;
Interleukin-1β;
Interleukin-1RN;
Gene polymorphism;
Gene chip
- From:
Chinese Journal of Microbiology and Immunology
2014;(3):186-193
- CountryChina
- Language:Chinese
-
Abstract:
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 increase in IL-1ra level (P<0.05).There was no significant difference in the serum level of IL-1βamong IL-1B-511CC carriers from each group ( P>0.05).The frequency of IL-1B-511TT genotype (P<0.05, OR=1.55, 95% CI =1.10-2.18) and IL-1B-511T allele (P<0.05,OR=1.31,95% CI=1.05-1.63) in patients with HCV infection were signifi-cantly higher than those in healthy controls .IL-1B-511C/T SNP showed a significant association with the outcomes of HCV infection (P<0.005).Compared with IL-1B-511CC and IL-1B-511CT, IL-1B-511TT was a major risk factor for mild and moderate Hepatitis C [ OR=2.17 ( 1.48-3.19 ) ] , severe Hepatitis C [OR=2.11(1.05-4.26)], cirrhosis [OR=2.98(1.77-4.99)] and HCC [4.33(2.16-8.67)].IL-1B-511 T allele was significantly associated with mild and moderate Hepatitis C [ 1.80 ( 1.38-2.36 ) ] , severe Hepatitis C [1.80(1.08-3.01)], cirrhosis [2.62(1.76-3.89)] and HCC [3.49(1.96-6.23)].The fre-quency of IL-1B-511T allele showed significant difference among each group (P<0.005).No association was found between any of the other polymorphisms and HCV infection .Conclusion The serum level of IL-1βand IL-1ra were significantly associated with HCV infection .IL-1B-511T allele in patients with HCV in-fection up-regulated the serum level of IL-1β.IL-1B-511TT and IL-1B-511T allele were major risk factors for mild and moderate Hepatitis C, severe Hepatitis C, cirrhosis and HCC, but IL-1B-511CC/C had oppo-site effects.
