IL-10 and TNF-α polymorphisms and the recovery from HCV infection

Lio, Domenico; Caruso, Calogero; Stefano, R. Di; Romano, Giuseppina Colonna; Ferraro, Donatella; Scola, Letizia; Crivello, Antonio; Licata, Anna; Valenza, Lilli Mario; Candore, Giuseppina; Craxı̀, Antonio; Almasio, Piero Luigi

doi:10.1016/s0198-8859(03)00080-6

Cited by 87 publications

(71 citation statements)

References 47 publications

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“…[12][13][14] Several groups have reported an association between IL-10 promotor polymorphism and outcome of HCV infection with diverse results. [42][43][44][45] In our HCV genotype-1 patients we could not find an association between the presence of IL10-R1 variants and response to antiviral therapy. In addition there was no difference in allele frequencies comparing control individuals and patients with CHC indicating no role for the polymorphism in disease susceptibility.…”

Section: Discussionmentioning

confidence: 99%

Bi-allelic presence of the interleukin-10 receptor 1 G330R allele is associated with cirrhosis in chronic HCV-1 infection

et al. 2005

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Immune response to viral infection is an important determinant of liver injury in chronic hepatitis C (CHC). Experimental and clinical data suggest a protective role of interleukin-10 (IL-10) in hepatic fibrogenesis. The significance of two SNPs of the interleukin-10 receptor 1 (IL-10R1), S138G (SNP3) and G330R (SNP4) was investigated on (i) susceptibility to CHC, (ii) progression of hepatic fibrosis and (iii) response to interferon/ribavirin therapy. DNA and liver biopsies were obtained from 212 patients with HCV (hepatitis C virus)-genotype-1 infection. The allele frequencies were 0.17 for SNP3 and 0.33 for SNP4, both of which were indifferent from healthy controls (0.17 and 0.32, respectively). Stage 1 liver fibrosis was found in 22 cases (10.4%), stage 2 in 108 (50.9%), stage 3 in 27 (12.8%), and stage 4 (cirrhosis) in 55 (25.9%). An association was found between the SNP4 allele and the presence of cirrhosis (P ¼ 0.01). Homozygous SNP4 individual variants segregated within the cirrhosis group (P ¼ 0.03). We found neither an association with SNP3 nor with the necroinflammatory disease activity (as measured by ALT levels) nor with the response to antiviral therapy. Our work implies that IL-10R1 SNP4 is a recessively inherited risk factor for hepatic cirrhosis in HCV genotype-1 infection.

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Section: Discussionmentioning

confidence: 99%

Bi-allelic presence of the interleukin-10 receptor 1 G330R allele is associated with cirrhosis in chronic HCV-1 infection

et al. 2005

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“…This study also found À863A to be associated with HCV clearance. 13 The TNF gene has been examined in many other diseases, and À863A has been associated with diseases related to increased immune activation including Crohn's disease 19 and human T-cell lymphotrophic virus-1 uveitis. 20 Other studies of HCV have not noted this association, but most were small and did not examine the SNP at À863.…”

Section: Discussionmentioning

confidence: 99%

“…Three of the promoter SNPs at À863, À308, and À238 have been studied in HCV infection. The SNP À863C/C has been associated with viral persistence, 13 and the SNPs at À238 and À308 have had inconsistent associations with various HCV outcomes. [14][15][16] No association has been found between TNF SNPs and response to HCV treatment thus far.…”

Section: Introductionmentioning

confidence: 99%

An analysis of tumor necrosis factor α gene polymorphisms and haplotypes with natural clearance of hepatitis C virus infection

et al. 2004

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The cytokine tumor necrosis factor alpha (TNF-a) is important in generating an immune response against a hepatitis C virus (HCV) infection. The functions of TNF-a may be altered by single-nucleotide polymorphisms (SNPs) in its gene, TNF. We hypothesized that SNPs in TNF may be important in determining the outcome of an HCV infection. To test this hypothesis, we typed nine TNF SNPs in a cohort of individuals with well-defined HCV outcomes. Three of these SNPs were typed in a second cohort. Data were analyzed using logistic regression stratifying by ethnicity, since rates of HCV clearance differ in black subjects versus white subjects. The SNP À863A was associated with viral clearance in black subjects (odds ratios (OR) 0.52, 95% confidence interval (CI) 0.29-0.93). Furthermore, the common wild-type haplotype À863C/À308G was associated with viral persistence in black subjects (OR 1.91, 95% CI 1.24-2.95). These findings were independent of linkage with human leukocyte antigen (HLA) alleles. Further study of this polymorphism and haplotype is needed to understand these associations and the role of TNF-a in determining outcomes of HCV infection.

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“…104,[111][112][113][114][115] However, two studies have appeared that did find an association of TNF SNPs with HCV. 116,117 The latter study 117 is curious not because of the reported higher occurrence of the À238A allele among chronic HCV patients, but because the reported frequency in a healthy control group (n ¼ 99) drops from 7 117 to 3.5% in an article published concurrently by the same group. 102 Septic shock Due to the well-known role of TNF in sepsis, the prospect of identifying functional variants of this gene was very attractive.…”

Section: Leprosymentioning

confidence: 99%

Is there a future for TNF promoter polymorphisms?

2004

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The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied À308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.

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IL-10 and TNF-α polymorphisms and the recovery from HCV infection

Cited by 87 publications

References 47 publications

Bi-allelic presence of the interleukin-10 receptor 1 G330R allele is associated with cirrhosis in chronic HCV-1 infection

Bi-allelic presence of the interleukin-10 receptor 1 G330R allele is associated with cirrhosis in chronic HCV-1 infection

An analysis of tumor necrosis factor α gene polymorphisms and haplotypes with natural clearance of hepatitis C virus infection

Is there a future for TNF promoter polymorphisms?

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