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The Impact of IL28B Genotype and Liver Fibrosis on the Hepatic Expression of IP10, IFI27, ISG15, and MX1 and Their Association with Treatment Outcomes in Patients with Chronic Hepatitis C.

Domagalski K, Pawłowska M, Kozielewicz D, Dybowska D, Tretyn A, Halota W - PLoS ONE (2015)

Bottom Line: We found no differences in IP10 expression between the IL28B genotypes (P > 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007).We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004).The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10.

View Article: PubMed Central - PubMed

Affiliation: Centre For Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Toruń, Poland.

ABSTRACT
The strong impact of interleukin 28B (IL28B) polymorphisms on sustained virological response (SVR) after peginterferon and ribavirin treatment in patients with chronic hepatitis C (CHC) is well-known. We investigated IL28B variability and hepatic expression of IP10, IFI27, ISG15, and MX1 in CHC patients, the relation of each with their clinical characteristics, and how they associated with responses to combined therapy. Genotyping and gene expression analysis were conducted in a selected cohort of treatment-naïve patients who underwent interferon and ribavirin treatment. Differential expression of IP10, IFI27, ISG15, and MX1 genes was assessed from pretreatment liver biopsies using quantitative PCR. Histopathological evaluation of liver specimens was performed on the basis of the Scheuer's modified scale. We showed that hepatic IFI27, ISG15, and MX1 expression was lower in the IL28B CC 12979860 and TT rs8099917 groups than in the CT-TT rs12979860 and TG-GG rs8099917 groups (P < 0.001). We found no differences in IP10 expression between the IL28B genotypes (P > 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007). We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004). Additionally, the expression levels of IP10, IFI27 and ISG15, but not MX1, were significantly higher in non-SVR patients than in SVR patients. The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10. Silencing of IP10 is positive and independent from IL28B prediction of SVR, which is strongly associated with liver fibrosis in CHC patients.

No MeSH data available.


Related in: MedlinePlus

The relationship between IL28B genotypes and expression levels of IP10, IFI27, ISG15, and MX1.The relationship between rs12979860 (A) and rs8099917 (B) genotypes and expression levels of IP10, IFI27, ISG15, and MX1 in the livers of CHC patients is shown. The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels.
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pone.0130899.g001: The relationship between IL28B genotypes and expression levels of IP10, IFI27, ISG15, and MX1.The relationship between rs12979860 (A) and rs8099917 (B) genotypes and expression levels of IP10, IFI27, ISG15, and MX1 in the livers of CHC patients is shown. The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels.

Mentions: In this study, we found that CC rs12979860 and TT rs8099917 genotypes were significantly associated with decreased expression of IFI27, ISG15 and MX1, compared to patients with CT-TT rs12979860 or TG-GG rs8099917 genotypes (P < 0.001 for all; Fig 1). The largest differences were observed in the expression of IFI27; we observed that rs12979860, more strongly than rs8099917, differentiates the expression of the analyzed genes. In contrast, the expression of IP10 was not related to the IL28B CC/CT-TT rs12979860 and TT/TG-GG rs8099917 genotypes. Though there were no statistically significant differences in IP10 expression across the IL28B genotypes, IP10 gene activity was lower in patients carrying homozygous genotypes for the major alleles of IL28B, with the greatest variation between groups analyzed for rs12979860.


The Impact of IL28B Genotype and Liver Fibrosis on the Hepatic Expression of IP10, IFI27, ISG15, and MX1 and Their Association with Treatment Outcomes in Patients with Chronic Hepatitis C.

Domagalski K, Pawłowska M, Kozielewicz D, Dybowska D, Tretyn A, Halota W - PLoS ONE (2015)

The relationship between IL28B genotypes and expression levels of IP10, IFI27, ISG15, and MX1.The relationship between rs12979860 (A) and rs8099917 (B) genotypes and expression levels of IP10, IFI27, ISG15, and MX1 in the livers of CHC patients is shown. The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482747&req=5

pone.0130899.g001: The relationship between IL28B genotypes and expression levels of IP10, IFI27, ISG15, and MX1.The relationship between rs12979860 (A) and rs8099917 (B) genotypes and expression levels of IP10, IFI27, ISG15, and MX1 in the livers of CHC patients is shown. The y-axis shows the relative unit of a given gene, normalized to GAPDH in log scale, as a box plot displaying the 10th, 25th, 50th, 75th, and 90th percentiles of expression levels.
Mentions: In this study, we found that CC rs12979860 and TT rs8099917 genotypes were significantly associated with decreased expression of IFI27, ISG15 and MX1, compared to patients with CT-TT rs12979860 or TG-GG rs8099917 genotypes (P < 0.001 for all; Fig 1). The largest differences were observed in the expression of IFI27; we observed that rs12979860, more strongly than rs8099917, differentiates the expression of the analyzed genes. In contrast, the expression of IP10 was not related to the IL28B CC/CT-TT rs12979860 and TT/TG-GG rs8099917 genotypes. Though there were no statistically significant differences in IP10 expression across the IL28B genotypes, IP10 gene activity was lower in patients carrying homozygous genotypes for the major alleles of IL28B, with the greatest variation between groups analyzed for rs12979860.

Bottom Line: We found no differences in IP10 expression between the IL28B genotypes (P > 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007).We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004).The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10.

View Article: PubMed Central - PubMed

Affiliation: Centre For Modern Interdisciplinary Technologies, Nicolaus Copernicus University, Toruń, Poland.

ABSTRACT
The strong impact of interleukin 28B (IL28B) polymorphisms on sustained virological response (SVR) after peginterferon and ribavirin treatment in patients with chronic hepatitis C (CHC) is well-known. We investigated IL28B variability and hepatic expression of IP10, IFI27, ISG15, and MX1 in CHC patients, the relation of each with their clinical characteristics, and how they associated with responses to combined therapy. Genotyping and gene expression analysis were conducted in a selected cohort of treatment-naïve patients who underwent interferon and ribavirin treatment. Differential expression of IP10, IFI27, ISG15, and MX1 genes was assessed from pretreatment liver biopsies using quantitative PCR. Histopathological evaluation of liver specimens was performed on the basis of the Scheuer's modified scale. We showed that hepatic IFI27, ISG15, and MX1 expression was lower in the IL28B CC 12979860 and TT rs8099917 groups than in the CT-TT rs12979860 and TG-GG rs8099917 groups (P < 0.001). We found no differences in IP10 expression between the IL28B genotypes (P > 0.05); in contrast, IP10 expression was significantly affected by the progression of fibrosis (P = 0.007). We showed that the rs12979860 CC genotype was associated with successful treatment when compared to the rs12979860 CT-TT genotype (P = 0.004). Additionally, the expression levels of IP10, IFI27 and ISG15, but not MX1, were significantly higher in non-SVR patients than in SVR patients. The effect of variation in IL28B on the results of IFN-based treatment may be associated with changes in IFI27 and ISG15, but not with IP10. Silencing of IP10 is positive and independent from IL28B prediction of SVR, which is strongly associated with liver fibrosis in CHC patients.

No MeSH data available.


Related in: MedlinePlus