Interleukin-6 gene polymorphisms and susceptibility to liver diseases

Wang, Xuehan; Yan, Zhijie; Ye, Qingjian

doi:10.1097/md.0000000000018408

Cited by 22 publications

(25 citation statements)

References 51 publications

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“…Similarly, a meta-analysis indicated that patients carrying G allele of IL-6 (rs1800795) may be more likely to suffer from liver diseases, which was ethnic-dependent. [ 21 ] Patients carrying IL-6 G allele were found to have high IL-6 expression in plasma and were more likely to cause persistent HCV infection. [ 22 ] In addition, other cytokines such as IL-1α and IFN-inducible protein-10 were also reported to have the potential to be the biomarkers for prognostic of HCV infection.…”

Section: Discussionmentioning

confidence: 99%

Association of cytokine gene polymorphisms with chronic hepatitis C virus genotype 1b infection in Chinese Han population

Jing¹,

Wang

Jiang

et al. 2020

Medicine

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Cytokines are extensively involved in the process of hepatitis C virus (HCV) infection and take a crucial part in host immune regulation. We aimed to explore the potential correlation of cytokine single nucleotide polymorphisms (SNPs) with HCV susceptibility and response rate of interferon (IFN)-based antiviral therapy in Chinese Han population. A case–control genetic association study was conducted between 198 patients with chronic HCV genotype 1b infection and 142 healthy controls. Genetic polymorphisms of TNF-α (rs1800629), TGF-β (rs1800469), IL-10 (rs1800896, rs1800871, and rs1800872), IL-6 (rs1800795, rs1800796), IFN-γ (rs2430561), and IL-28B (rs12979860, rs12980275, and rs8099917) were analyzed by MassARRAY SNP technology. Patients were treated with IFNα-2b or pegylated-IFNα-2a plus ribavirin for 48 weeks. Sustained virological response (SVR) was assessed 6 months after the completion of the treatment. The IL-28B rs12979860-CC (odds ratio [OR] = 4.35, 95% confidence interval [CI]: 1.69–11.21, P = .001), rs12980275-AA (OR = 3.41, 95% CI: 1.08–10.76, P = .028), and rs8099917-TT (OR = 3.86, 95% CI: 1.49–10.12, P = .004) were significantly associated with SVR, and IL-10 rs1800871-TT (OR = .50, 95% CI: 0.25–1.00, P = .049) and rs1800872-AA (OR = .50, 95% CI: 0.25–1.00, P = .049) were also significant for SVR. No association was found between the cytokine SNPs and HCV susceptibility. Additionally, multivariate analysis showed that low baseline viral load (OR = 3.63, 95% CI: 1.01–13.02, P = .048), pegylated-IFN (OR = 9.68, 95% CI: 1.14–82.13, P = .037) and rs12979860-CC (OR = 6.08, 95% CI: 2.00–18.46, P = .001) were independent factors for SVR. IL-28 and IL-10 gene polymorphisms played an important role in predicting host response to IFN-based antiviral therapy in HCV genotype 1b infection.

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Section: Discussionmentioning

confidence: 99%

Association of cytokine gene polymorphisms with chronic hepatitis C virus genotype 1b infection in Chinese Han population

Jing¹,

Wang

Jiang

et al. 2020

Medicine

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“…Although, several investigations have shown that subjects carrying the GC and CC genotypes of IL-6 SNP had a decreased risk of type 2 diabetes mellitus[ 34 - 38 ], the association has not found by others[ 34 , 39 ], which may be due to the differences in the study designs and/or genetic ancestry of the populations. Concerning the chronic liver diseases, the IL-6-174G/C polymorphism has been associated with both fibrosis progression and hepatocellular carcinoma development[ 41 , 62 , 63 ] in patients with CHC. The majority of the studies has verified an association between the presence of the high producer genotype (GG) and poor outcome in patients with the hepatopathy[ 31 , 32 , 40 , 41 , 62 , 63 ].…”

Section: Discussionmentioning

confidence: 99%

“…Concerning the chronic liver diseases, the IL-6-174G/C polymorphism has been associated with both fibrosis progression and hepatocellular carcinoma development[ 41 , 62 , 63 ] in patients with CHC. The majority of the studies has verified an association between the presence of the high producer genotype (GG) and poor outcome in patients with the hepatopathy[ 31 , 32 , 40 , 41 , 62 , 63 ].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6-174G/C polymorphism is associated with a decreased risk of type 2 diabetes in patients with chronic hepatitis C virus

Silva

Vieira

Melo

et al. 2020

WJH

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BACKGROUND Chronic hepatitis C (CHC) is associated with type 2 diabetes mellitus. Although the pathogenesis remains to be elucidated, a growing evidence has suggested a role of pro-inflammatory immune response. Increased serum concentrations of Interleukin 6 (IL-6) have been associated with insulin resistance, type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection. AIM To investigate the frequency of IL-6-174G/C (rs1800795) single nucleotide polymorphism (SNP) in CHC patients and in healthy subjects of the same ethnicity. Associations between type 2 diabetes mellitus (dependent variable) and demographic, clinical, nutritional, virological and, IL-6 genotyping data were also investigated in CHC patients. METHODS Two hundred and forty-five patients with CHC and 179 healthy control subjects (blood donors) were prospectively included. Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association. Clinical, biochemical, histological and radiological methods were used for the diagnosis of the liver disease. IL-6 polymorphism was evaluated by Taqman SNP genotyping assay. The data were analysed by logistic regression models. RESULTS Type 2 diabetes mellitus, blood hypertension and liver cirrhosis were observed in 20.8% (51/245), 40.0% (98/245) and 38.4% (94/245) of the patients, respectively. The frequency of the studied IL-6 SNP did not differ between the CHC patients and controls ( P = 0.81) and all alleles were in Hardy-Weinberg equilibrium ( P = 0.38). In the multivariate analysis, type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL-6-174 (OR = 0.42; 95%CI = 0.22-0.78; P = 0.006) and positively associated with blood hypertension (OR = 5.56; 95%CI = 2.79-11.09; P < 0.001). CONCLUSION This study was the first to show that GC and CC genotypes of IL-6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients chronically infected with hepatitis C virus. The identification of potential inflammatory mediators involved in the crosstalk between hepatitis C virus and the axis pancreas-liver remains important issues that deserve further investigations.

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“…In NAFLD, IL-6 may enhance hepatic repair and regeneration, however, it might also be involved in inducing insulin resistance and stimulating hepatocyte apoptosis, thus contributing to NASH progression (42,44). Indeed IL-6 gene polymorphisms have been associated with an increased susceptibility to chronic liver disease (45).…”

Section: Discussionmentioning

confidence: 99%

Sex differences in the progression from NAFL to NASH: a functional meta-analysis of transcriptomic studies

Català-Senent

Hidalgo

Berenguer

et al. 2020

Preprint

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Background & aims Sex differences in non-alcoholic fatty liver disease (NAFLD) are well known and yet, most of the studies available in the literature do not include this factor when analysing the data. Here we present a functional meta-analysis of NAFLD studies to detect the molecular mechanisms involved in its progression, distinguishing any differences relative to patient sex. Methods: We systematically reviewed the Gene Expression Omnibus (GEO) database functional Gene Ontology (GO) terms detailed in transcriptomic studies, following the PRISMA statement guidelines. For each study, we compared the progression from steatosis (NAFL) to steatohepatitis (NASH) in premenopausal women and men using a dual strategy: a gene-set analysis and a pathway activity analysis. The functional results of all the studies were integrated in a meta-analysis used to detect functions that were differentially affected in these groups, according to these two methods. Results: A total of 105 abstracts were reviewed and 7 studies, which included 624 patients, were finally analysed. The meta-analyses highlighted significant functions in both sexes. In premenopausal women, the overrepresented functions referred to DNA regulation, vinculin binding, interleukin 2 (IL-2) responses, negative regulation of neuronal death, and the transport of ions and cations. In men, they referred to the negative regulation of IL-6 and the establishment of planar polarity involved in neural tube closure. Conclusions: Our meta-analysis of this transcriptomic data provides a powerful approach to identify sex differences in the progression from NAFL to NASH. We detected relevant biological functions and molecular terms that were affected differently between premenopausal women and men. Changes in the immune responsiveness between men and women with NAFLD suggested that women have a more immune tolerant milieu while men have an impaired liver regenerative response. These results open the door to more pathophysiological studies into the differential role of IL-2 and IL-6 in NAFLD, and eventually to personalised treatments for this disease. Lay summary: Progression from NAFL to NASH differently affects cellular functions in women and men. Here we systematically reviewed publicly available transcriptomic data and then performed a meta-analysis to find these affected functions. Thus, we identified 13 biological functions implicated in the progression of NAFLD that were differentially affected by sex.

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Interleukin-6 gene polymorphisms and susceptibility to liver diseases

Cited by 22 publications

References 51 publications

Association of cytokine gene polymorphisms with chronic hepatitis C virus genotype 1b infection in Chinese Han population

Association of cytokine gene polymorphisms with chronic hepatitis C virus genotype 1b infection in Chinese Han population

Interleukin-6-174G/C polymorphism is associated with a decreased risk of type 2 diabetes in patients with chronic hepatitis C virus

Sex differences in the progression from NAFL to NASH: a functional meta-analysis of transcriptomic studies

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