An Investigation of Polymorphism in the Interleukin-10 Gene Promoter.
Interleukin-10 (IL-10) has been described as an anti-inflammatory cytokine and B-cell proliferation factor and has been implicated in autoimmunity, tumorigenesis and transplantation tolerance. We have identified three single base pair substitutions in the IL-10 gene promoter and have investigated whether this polymorphism correlates with IL-10 protein production in vitro.
Available from: Beatris Maria Vidales-Braz
- "Three biallelic single-nucleotide polymorphisms (SNPs) were described in the promoter region -1082 (G/A), -819 (C/T) and -592 (C/A). There is linkage disequilibrium between the SNPs -819 and -592 because the C allele of -819 is always present when there is a C allele in -592, whereas the T allele is always present in -819 when the A allele is in -592  . "
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ABSTRACT: Interleukin-10 (IL-10) is a cytokine that plays an important role in the regulation of the immune system. Gene polymorphisms of IL-10 have been associated with the different expression levels of this cytokine. In hepatitis C virus infection, IL-10 appears to interfere with the progression of disease, viral persistence and the response to therapy. This study investigated genetic variability in the IL-10 gene promoter between patients infected with hepatitis C virus (HCV) and healthy individuals, associating the frequency of polymorphisms with different aspects of viral infection. This is a case-control study with 260 patients who were infected with HCV and 260 healthy individuals. Genotyping of the polymorphisms was performed using the technique of amplification refractory mutation system PCR (ARMS-PCR) for regions of the IL-10 gene promoter (-1082 G/A, -819 C/T, -592 C/A). The frequencies of alleles and genotypes related to polymorphisms in the IL-10 gene promoter showed a higher frequency of the G allele and genotype GG in the -1082 region between the infected group and the control group (p=0.005 and p=0.001, respectively), whereas the AA genotype was significantly more frequent in the control group. The frequencies of the haplotypes GTA and GCC were higher in the group of infected individuals, whereas the haplotype ATA was more frequent in the healthy group (p<0.006). It was also observed that the genotypes GG and AG in the region -1082 were significantly more frequent among patients infected with HCV who were in advanced stages of fibrosis and cirrhosis (p=0.042). No association was observed between polymorphisms of IL-10 and sustained virologic response (SVR).
Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Cytokine 06/2015; 14(2). DOI:10.1016/j.cyto.2014.12.022 · 2.66 Impact Factor
Available from: Sabrina Zidi
- "IL-10 gene promoter and intron polymorphisms as genetic biomarkers of cervical cancer susceptibility among Tunisians. Cytokine (2015), http://dx.doi.org/10.1016/j.cyto.2015.05.028 has been reported that several important polymorphic sites in the IL-10 gene, appears to be responsible with modulated levels of IL-10   . The association of IL-10 promoter SNPs with CC has been reported by several studies, but with inconclusive findings     . "
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ABSTRACT: We investigated the association between polymorphisms in the promoter and intron regions of the interleukin-10 (IL-10) gene with the risk of cervical cancer (CC) in Tunisian patients and control women.
Study subjects comprised 86 CC cases and 126 control women. Genotyping of IL-10 intron (rs3024491, rs3024490) and promoter (rs1800872, rs1800871, rs1800896) variants was done by real-time PCR, with defined clusters.
The minor allele frequencies of the five tested IL-10 SNPs were not significantly different between cervical cancer cases and control women. However, significantly higher frequencies of homozygous minor allele-carriers in cases was seen for rs3024490 (P=0.023), rs1800872 (P=0.037), and rs1800871 (P=0.028). IL-10 serum levels were significantly reduced in rs3024490 T/T vs. G/G genotype carriers, and in rs1800871 T/T than C/C genotype carriers. While carriage of rs1800872 and rs3024491 minor allele was associated with reduced IL-10 secretion, this was not statistically significant. Haploview analysis demonstrated high linkage disequilibrium (LD) among the IL10 SNPs studied, and only seven haplotypes were common, capturing 98.8% of the total possible haplotypes. Reduced frequency of haplotypes GTCCA (P<0.001) and TGATG (P<0.001) was seen in cervical cancer cases than in control women, thus conferring disease protection nature to these haplotype. This association remained significant for GTCCA (Pc=0.006) and TGATG (P=0.045) after correcting for multiple comparisons.
Specific IL-10 variants (rs3024490, rs1800872, and rs1800871) and haplotype (GTCCA and TGATG) may contribute to the development of cervical cancer among Tunisian women.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Cytokine 06/2015; 76(2). DOI:10.1016/j.cyto.2015.05.028 · 2.66 Impact Factor
Available from: Zhi-ming Dai
- "The human gene encoding IL-10 is located on chromosome 1 (1q31–1q32) and spans about 4.7 kb (Turner et al., 1997). The IL-10 gene promoter is highly polymorphic and the polymorphisms have been associated with diseases by regulating the transcription of IL-10 RNA and the expression of IL-10. "
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ABSTRACT: Previous studies investigated the associations of interleukin-10 (IL-10) polymorphisms with different types of cancer, indicating an influence on cancer risk. IL-10-3575T>A (rs1800890) has been studied concerning a potential implication in terms of some cancer site risks, but the results from single studies are contradictory.
Eligible articles were identified by a search of the PubMed, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) databases until November 30, 2014. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the cancer risk by cancer sites, ethnicity, and other study features.
We identified 15 published studies to research the link of the IL-10-3575T>A polymorphism with cancer risk. Our meta-analysis indicated that the IL-10-3575T>A polymorphism has a significant association with decreased melanoma risk in the heterozygote model (OR=0.67, 95% CI=0.49-0.92, p=0.02) and dominant model (OR=0.70, 95% CI=0.52-0.95, p=0.01), but increased diffuse large B-cell lymphoma (DLBCL) risk in all the different genetic models.
Our analysis suggests that the IL-10-3575T>A mutation may associate with melanoma and DLBCL and exert a differential effect in different cancer sites. However, other factors may influence the association, and large-scale multicenter with adequate methodological quality studies are needed to confirm the impact on cancer susceptibility.
Genetic Testing and Molecular Biomarkers 05/2015; 19(6). DOI:10.1089/gtmb.2015.0024 · 1.46 Impact Factor
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