Manipulation of Interleukin-6

• Published in: PloS one Vol. 17; no. 10; p. e0275834
• Main Authors: Badshah, Yasmin, Shabbir, Maria, Khan, Khushbukhat, Fatima, Maha, Majoka, Iqra, Aslam, Laiba, Munawar, Huda
• Format: Journal Article
• Language: English
• Published: Public Library of Science 10.10.2022
• Subjects: Analysis; Diagnosis; Genetic aspects; Genetic transcription; Health aspects; Interleukin-6; Liver cancer; Transforming growth factors; Pakistan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0275834

Hepatocellular carcinoma (HCC) is the most common liver malignancy. Early diagnosis of HCC has always been challenging. This study aims to assess the pathogenicity and the prevalence of IL-6 -174G/C (rs1800795) and TGF[beta]-1 +29C/T (rs1800470) polymorphisms in HCV-infected HCC patients. Experimental strategies are integrated with computational approaches to analyse the pathogenicity of the TGF[beta]-1 +29C/T and IL-6-174 G/C polymorphisms in HCV-induced HCC. AliBaba2 was used to predict the effect of IL-6-174 G/C on transcription factor binding site in IL-6 gene. Structural changes in the mutant TGF[beta]-1 structure were determined through project HOPE. To assess the polymorphic prevalence of IL-6 -174G/C and TGF[beta]-1 +29C/T genotypes in HCC and control subjects, amplification refractory mutation system PCR (ARMS-PCR) was performed on 213 HCC and 216 control samples. GraphPad Prism version 8.0 was used for the statistical analysis of the results. In-silico analysis revealed the regulatory nature of both IL-6 -174G/C and TGF[beta]-1 +29C/T polymorphisms. ARMS-PCR results revealed that the individuals carrying TT genotype for TGF[beta]-1 gene have an increased risk of developing HCC (p<0.0001, OR = 5.403, RR = 2.062) as compared to individuals with CT and CC genotype. Similarly, GC genotype carriers for IL-6 gene exhibit an increased risk of HCC susceptibility (p<0.0001, OR = 2.276, RR = 1.512) as compared to the people carrying the GG genotype. Genotype TT of TGF[beta]-1 gene and genotype GC of IL-6 gene are found to be associated with HCV-induced HCC. IL-6 polymorphism may alter its transcription that leads to its pathogenicity. TGF[beta]-1 polymorphism may alter protein structure stability.