Effect of IL-12B, IL-2, TGF-β1, and IL-4 Polymorphism and Expression on Hepatitis B Progression

被引:41
作者
Saxena, Roli [1 ]
Chawla, Yogesh Kumar [2 ]
Verma, Indu [1 ]
Kaur, Jyotdeep [1 ]
机构
[1] Postgrad Inst Med Educ & Res, Dept Biochem, Chandigarh 160012, India
[2] Postgrad Inst Med Educ & Res, Dept Hepatol, Chandigarh 160012, India
关键词
CYTOKINE GENE POLYMORPHISMS; TRANSFORMING-GROWTH-FACTOR; HEPATOCELLULAR-CARCINOMA RISK; VIRUS-INFECTION; P40; GENE; GROWTH-FACTOR-BETA-1; PROMOTER POLYMORPHISM; IL12B POLYMORPHISMS; CHINESE POPULATION; MEDIATED DISEASE;
D O I
10.1089/jir.2013.0043
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The hepatitis B virus (HBV) infection-induced chronic inflammation is considered to be the major etiological factor for HBV-related disease chronicity. Cytokines act as the key coordinators of the inflammatory responses involved in HBV disease pathogenesis. The present study assessed association among IL-12B(+1188), IL-2(-330), TGF-β1(-509), and IL-4(-590) genotypes; mRNA; and protein levels with HBV-hepatocellular carcinoma (HCC) risk in India. For this, 403 subjects (153 controls, 67 inactive HBV-carriers, 62 chronic-active HBV patients, 62 HBV-cirrhotics, and 59 HBV-HCC ssubjects) were enrolled in the study. The genotyping was carried by polymerase chain reaction (PCR)-restriction fragment length polymorphism (IL-12+1188A/C, IL-2-330T/G, and TGF-β1-509C/T), and allele specific (AS)-polymerase chain reaction (IL-4-590C/T). Enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction methods were used for assessing protein and the mRNA expression, respectively, of the mentioned cytokines. The study revealed that the IL-12B(+1188) CC genotype shared a significant positive association with hepatitis, among controls. While, in the case of IL-2(-330), both the TG and GG genotypes were not significantly associated with HCC risk. The TGF-β1(-509) TT genotype acted as a potential protective factor for cirrhosis and the HCC risk, among carriers. On the contrary, the IL-4(-590) CT genotype was found to be a vital protective factor for the development of hepatitis, among carriers. Besides, IL-12B, TGF-β1, and IL-2 seem to be majorly involved in the development of HCC, while, IL-4 might be responsible for the progression of the HBV disease till cirrhosis development. These initial findings are indicative of the vital role of genotypes and/or levels of IL-12B, IL-2, IL-4, and TGF-β1 in HBV disease chronicity in Indian population. © 2014 Mary Ann Liebert, Inc..
引用
收藏
页码:117 / 128
页数:12
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