title: Effect of IL-12B, IL-2, TGF-β1, and IL-4 polymorphism and expression on hepatitis B progression.
abstract: 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.
authors.affiliation: 1 Department of Biochemistry, Postgraduate Institute of Medical Education and Research , Chandigarh, India .
authors.forename: Roli
authors.initials: R
authors.lastname: Saxena
authors.forename: Yogesh Kumar
authors.initials: YK
authors.lastname: Chawla
authors.forename: Indu
authors.initials: I
authors.lastname: Verma
authors.forename: Jyotdeep
authors.initials: J
authors.lastname: Kaur
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000276:immunology*; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007194:India; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D053773:Transforming Growth Factor beta1; D018664:Interleukin-12; D015847:Interleukin-4