IL28B Polymorphisms and Clinical Implications for Hepatitis C Virus Infection in Uzbekistan

Abstract

AimsGenome-wide association studies highlighted single nucleotide polymorphisms (SNPs) within the IFNL3/IL28B locus predict the treatment outcome for patients with HCV. Furthermore, SNPs in newly discovered IFNL4 are shown to have population-specific correlation with spontaneous clearance of HCV. The aim of this study was to examine the prevalence and clinical significance of the outlined SNPs in a population from Central Asia, a multi-ethnic region with a developing economy and a high prevalence of HCV infection.MethodsOne hundred and thirty-five chronic HCV patients from Uzbekistan were enrolled. DNA specimens were extracted from peripheral blood mononuclear cells and the IFNL3 SNPs (rs8099917, rs12979860) were genotyped by the Invader Plus assay, the TaqMan assay, and by direct sequence analysis. The IFL4 region (ss469415590) was sequenced.ResultsOf the 135 patients that completed 24 or 48 weeks of treatment with Peg-IFN-α plus RBV, 87.4% were of Central Asian (CA) ancestry and 12.6% were of Eastern European (EE) ancestry. A non-virological response was observed in 21.2% of CA and in 35.3% of EE, respectively (p<0.32). The rs12979860 was strongly associated with treatment response (OR, 5.2; 95% CI, 1.9–14.6; p<0.004) in the overall sample; however, SNP rs8099917 was the most predictive of outcome for CA group (OR, 6.9; 95% CI, 2.6–18.0; p<0.002). The allele frequency of IFNL4 SNP, ss469415590, was identical with that of rs12979860 in all samples.ConclusionsSNPs in IFNL3 and IFNL4 can be used to predict HCV treatment outcome in a population of Central Asian ancestry.

Relationship between IL28B gene rs8099917 polymorphism and SVR in Turkish patients with hepatitis C virus genotype 1

“…In the present study, when the HCV RNA levels analysed, neither SVR nor rs80999917 genotypes were associated by HCV RNA levels. These results are consistent with other studies, which presented similar results [29,36]. On the other hand, several studies reported mean HCV RNA level had a significantly higher in the carriers of rs8099917 G allele and the non-SVR group [22,27,32,35,40].…”

“…Asian and Caucasian patients with TT genotype had a 5.21-and a 2.54-fold greater chance of SVR than TT-negative patients [30]. The carriers of the nonresponders variants TG and GG had a higher risk for therapy failure than noncarriers [4,22,29,36]. This is in again agreement with our study; (OR, 11.10; 95% CI, 2.43-50.75; P < 0.001 for GG and OR, 4.00; 95% CI, 2.43-6.60; P < 0.001 for TG, respectively).…”

IL28Brs12980275 polymorphism shows association with response to treatment in Pakistani patients with Chronic Hepatitis C

“…Recently, a dinucleotide variant, ss469415590, in strong linkage disequilibrium with rs12979860 has been reported, which created a novel IFNL4 gene and has functional effects on the IL28B expression [Prokunina‐Olsson et al, ]. The identification of IFNL4 SNP has improved prediction rate of response to peg interferon and ribavirin therapy in HCV patients however, differences among various ethnic groups have been reported [Khudayberganova et al, ; Real et al, ]. Study of the ss469415590 and the IL28B SNPs genotyped in this study may help to better predict response to HCV treatment.…”

Interleukin 28B rs12979860 CT, rs12980275 GA, rs8099917 GT and TT genotypes are the Predictors of Rapid Viral Response in Hepatitis C Virus-Infected Patients

“…In Taiwan, not the rs12979860 but the rs8099917 TT genotype had benefit from a shorter duration of combination therapy in HCV-1 patients (33). In Uzbekistan, SNP rs8099917 was found the most predictive of outcome for Central Asians (18) and in chile, all the three genotypes (the IL28B rs12979860 CC, rs12980275 AA and rs8099917 TT) have been found frequent in patients with SVR compared to null responders (38%, 44% and 50% vs. 2%, 8.2% and 8.2%, respectively) (34). Two recent studies have failed to show such an association: status of IL-28B polymorphism neither affected nor had an impact on virologic response in France and Japan (35,36).…”

“…SNPs of the IL28B gene has been extensively described in the literature but allele frequencies, in particular rs809917, differs somewhat between world-wide populations (17,18,19,20). Therefore, the predictive power of SNPs may vary between different cohorts.…”