Association of Interleukin-4 (-590 C/T) and Interleukin-6 (-174 G/C) Polymorphism in Pathogenesis and Prognosis of Hepatitis C Virus Infection

Badshah, Yasmin; Arshad, Najma; Khan, M. Iqbal R.; Jannat, Arooma; Hayat, Hunza

doi:10.1089/jir.2018.0081

Cited by 4 publications

(6 citation statements)

References 28 publications

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“…However, it has been reviewed that spontaneous viral clearance after HCV infection was associated with GG genotype of IL6 −174 polymorphism 40 . However, in a further study, elevated viral load has been observed in HCV patients possessing GG and CC genotypes as compared with patients with GC genotype 41 . With respect to IL12B −1188 A/C (rs3212227) polymorphism, there have also been some arguments whether this SNP is associated with persistent viremia or clearance of HCV infection, and inconsistent observations were made 42 …”

Section: Discussionmentioning

confidence: 98%

Genetic variants in IL4RA, IL6, and IL12B genes and susceptibility to hepatitis B and C virus infections among Iraqi patients

Al-Saffar

Ad’hiah

2020

Journal of Medical Virology

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Hepatitis B and C viruses (HBV and HCV) are common causative pathogens of viral hepatitis. Progression of both infections is determined by virus‐ and host‐related factors. Cytokines are important host genetic factors that may have a predisposing role in HBV and HCV infections. This case‐control study evaluated the genetic association of IL4RA+1902 (rs1801275), IL6−174 (rs1800795), IL6−597 (rs1800797), and IL12B−1188 (rs3212227) variants with chronic HBV and HCV infections among Iraqi patients. A total of 220 viral hepatitis patients were enrolled in the study (113 HBV and 107 HCV), together with 141 healthy subjects. Sequence‐specific primer polymerase chain reaction assay was the genotyping method. Results revealed that under a dominant genetic model, IL6−174 variant was significantly associated with HBV infection, whereas no association with the HCV risk was reported. However, the risk for both infections was markedly associated with IL6−597 variant under recessive, dominant, and codominant genetic models. Estimation of IL6−174‐IL6−597 haplotypes depicted that G‐A haplotype was significantly associated with an increased risk to develop HBV infection, whereas a significantly decreased risk was associated with G‐G and C‐G haplotypes. For HCV, G‐G and C‐A haplotypes were significantly associated with risk of HCV infection. IL4RA+1902 and IL12B−1188 variants showed no association with HBV or HCV risk. Analysis of variance revealed no significant association between genotypes of the four determined single‐nucleotide polymorphisms and HBV or HCV viral load. In conclusion, the study supports the concept that IL6−597 variant is associated with susceptibility to HBV and HCV infections among Iraqis. The risk of HBV infection is further associated with IL6−174 variant.

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Section: Discussionmentioning

confidence: 98%

Genetic variants in IL4RA, IL6, and IL12B genes and susceptibility to hepatitis B and C virus infections among Iraqi patients

Al-Saffar

Ad’hiah

2020

Journal of Medical Virology

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“…A meta-analysis study has also confirmed a significant association of IL-6–174 G/C polymorphism with HCC susceptibility [ 62 ]. Some groups have studied the association of SNPs in IL-6 gene with the development of HCC in Pakistani population [ 26 , 63 ], however, none of these studies focused on the -174G/C polymorphism in HCV induced HCC. Badshah et al studied IL-6-174G/C polymorphisms in association with the pathogenesis and prognosis of HCV infection.…”

Section: Discussionmentioning

confidence: 99%

Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis

Badshah

Shabbir²,

Fatima³

et al. 2022

PLoS ONE

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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 TGFβ-1 +29C/T (rs1800470) polymorphisms in HCV-infected HCC patients. Experimental strategies are integrated with computational approaches to analyse the pathogenicity of the TGFβ-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 TGFβ-1 structure were determined through project HOPE. To assess the polymorphic prevalence of IL-6 -174G/C and TGFβ-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 TGFβ-1 +29C/T polymorphisms. ARMS-PCR results revealed that the individuals carrying TT genotype for TGFβ-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 TGFβ-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. TGFβ-1 polymorphism may alter protein structure stability.

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“…IL-6 (-174-G/C) polymorphism has been evaluated for its association with various inflammatory conditions such as rheumatoid arthritis (RA), hepatitis C (HCV) and allergy [27, 29, 32]. The GG genotype has been associated with the higher production of IL-6 along with being established as a risk genotype for various inflammatory conditions [27, 31].…”

Section: Discussionmentioning

confidence: 99%

“…Genotyping of IL-6 (-174-G/C) polymorphism was done through Amplification-Refractory Mutation System PCR (ARMS-PCR) using the primer sets (Macrogen, Seoul, South Korea) already reported in Badshah et. al., 2018 [32]. The results were analyzed using 2% agarose gel.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies revealed that GG and GC are prevalent in cases with allergy in comparison to CC genotype [28–31]. The association of IL-6 (-174-G/C) polymorphism has been established with various inflammatory conditions and has been associated with the prognosis and pathogenesis of the inflammatory disorders [32, 33]. SOCS3 activity is strictly controlled by IL-6 thus any alteration in IL-6 serum levels may affect SOCS3 expression and activity [34].…”

Section: Introductionmentioning

confidence: 99%

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Expression of suppressor of cytokine signaling 3 (SOCS3) and interleukin-6 (-174-G/C) polymorphism in atopic conditions

et al. 2019

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Hypersensitivity of the immune system is caused by elevated immunoglobulin E (IgE) levels in the serum, in response to a discrete allergen leading to allergic reactions. IgE-mediated inflammation is regulated by the cascade of defense related signaling molecules including interleukin-6 (IL-6) that plays pivotal role in the survival and maturation of mast cells during an allergic reaction. IL-6 mediated defense responses are tightly regulated by Suppressor of Cytokine Signaling 3 (SOCS3), an inhibitory molecules of Janus Kinase-Signal Transducers and Activators of Transcription (JAK-STAT) signaling, in a negative feedback mechanism. The given study focuses on the assessment of crosstalk between SOCS3 and IL-6 to unravel the molecular significance of SOCS3 and IL-6 in the diagnosis and prognosis of allergy. The expression study of SOCS3 through real-time PCR analysis revealed, a 5.9 mean fold increase in SOCS3 expression in atopic cases in comparison to control cases. Moreover, IL-6 has, also, been found significantly enhanced in the serum level of atopic cases (26.4 pg/ml) as compared to control cases (3.686 pg/ml). Female population was found to be at a higher risk to develop atopic condition than male population as females exhibited higher expression of both SOCS3 and IL-6 than males. Furthermore, the polymorphic study of IL-6 promoter region (IL-6 174-G/C) in atopic population has reasserted the importance of SOCS3 and IL-6 in the diagnosis and prognosis of allergy. Expression of SOCS3 and IL-6 serum levels were found to be highly correlated. Therefore establishing the role of IL-6 (-174-G/C) polymorphism on the expression of SOCS3 and IL-6 in atopic cases. Notably, the study established SOCS3 and IL-6 as potential targets for the diagnosis/prognosis of allergy and for the development of reliable therapeutic strategies to control atopic conditions in the near future.

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Association of Interleukin-4 (-590 C/T) and Interleukin-6 (-174 G/C) Polymorphism in Pathogenesis and Prognosis of Hepatitis C Virus Infection

Cited by 4 publications

References 28 publications

Genetic variants in IL4RA, IL6, and IL12B genes and susceptibility to hepatitis B and C virus infections among Iraqi patients

Genetic variants in IL4RA, IL6, and IL12B genes and susceptibility to hepatitis B and C virus infections among Iraqi patients

Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis

Expression of suppressor of cytokine signaling 3 (SOCS3) and interleukin-6 (-174-G/C) polymorphism in atopic conditions

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