Dataset Information

IL28B polymorphisms and clinical implications for hepatitis C virus infection in Uzbekistan.

ABSTRACT:

Aims

Genome-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.

Methods

One 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.

Results

Of the 135 patients that completed 24 or 48 weeks of treatment with Peg-IFN-? 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.

Conclusions

SNPs in IFNL3 and IFNL4 can be used to predict HCV treatment outcome in a population of Central Asian ancestry.

SUBMITTER: Khudayberganova D

PROVIDER: S-EPMC3963975 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

IL28B polymorphisms and clinical implications for hepatitis C virus infection in Uzbekistan.

Khudayberganova Dinara D Sugiyama Masaya M Masaki Naohiko N Nishida Nao N Mukaide Motokazu M Sekler Dildora D Latipov Renat R Nataliya Kan K Dildora Suyarkulova S Sharapov Said S Usmanova Guzal G Raxmanov Mahmarajab M Musabaev Erkin E Mizokami Masashi M

PloS one 20140324 3

<h4>Aims</h4>Genome-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 ...[more]

PMID: 24662995

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Project description:BACKGROUND:Recent clinical studies have shown that the presence of CC genotype in the rs12979860 region of IL28B gene is associated with an increase in the probability of spontaneous clearance of hepatitis C virus (HCV). Moreover, IL28B polymorphism seems to influence the probability of developing liver steatosis in chronic HCV patients. AIMS:The aims of our clinical study were 1) to verify the distribution of IL28B genotypes (CC, CT or TT) among subjects with spontaneous clearance of HCV infection and 2) to examine the correlation between IL28B polymorphism and hepatic steatosis among these subjects. METHODS AND PATIENTS:We enrolled 41 subjects with spontaneous resolution of HCV infection (detectable serum anti-HCV but undetectable HCV-RNA) and 134 healthy controls from the same geographical area. The IL28B single-nucleotide polymorphism (SNP) rs12979860 was genotyped by using a Pyrosequencing™ technique. The presence of steatosis was assessed by liver biopsy or ultrasound examination in the 41 study subjects. RESULTS:CC, CT and TT-genotypes of the SNP rs1979860 were found in 66%, 24% and 10% of the subjects who spontaneously cleared HCV and in 31%, 54% and 15% of controls, respectively (p?=?0.0003). Among the study subjects, females with CC-genotype were significantly more represented (p?=?0.02). Hepatic steatosis did not correlate with IL28B genotype (p?=?0,14) but only with a high body mass index (BMI) value (p?=?0.03). CONCLUSIONS:Female subjects carrying IL28B CC-genotype are significantly more represented among Italian patients who spontaneously cleared HCV infection. In addition, among these subjects, the presence of liver steatosis does not correlate with IL28B genotype but is solely related to the occurrence of high BMI. Thus, the association between IL28B polymorphism and steatosis in chronic HCV patients requires the presence of active HCV replication to occur, while in subjects who have cleared the infection, the mechanism(s) inducing liver steatosis are independent from IL28B profile.

Project description:BackgroundIn Uzbekistan, routine serologic testing has not been available to differentiate etiologies of acute viral hepatitis (AVH). To determine the age groups most affected by hepatitis E virus (HEV) during documented AVH epidemics, trends in AVH-associated mortality rate (MR) per 100,000 over a 15-year period and reported incidence of AVH over a 35-year period were examined.MethodsReported AVH incidence data from 1971 to 2005 and AVH-associated mortality data from 1981 to 1995 were examined. Serologic markers for infection with hepatitis viruses A, B, D, and E were determined from a sample of hospitalized patients with AVH from an epidemic period (1987) and from a sample of pregnant women with AVH from a non-epidemic period (1992).ResultsTwo multi-year AVH outbreaks were identified: one during 1975-1976, and one during 1985-1987. During 1985-1987, AVH-associated MRs were 12.3-17.8 per 100,000 for the general population. Highest AVH-associated MRs occurred among children in the first 3 years of life (40-190 per 100,000) and among women aged 20-29 (15-21 per 100,000). During 1988-1995 when reported AVH morbidity was much lower in the general population, AVH-associated MRs were markedly lower among these same age groups. In 1988, AVH-associated MRs were higher in rural (21 per 100,000) than in urban (8 per 100,000) populations (RR 2.6; 95% CI 1.16-5.93; p < 0.05). Serologic evidence of acute HEV infection was found in 280 of 396 (71%) patients with AVH in 1987 and 12 of 99 (12%) pregnant patients with AVH in 1992.ConclusionIn the absence of the availability of confirmatory testing, inferences regarding probable hepatitis epidemic etiologies can sometimes be made using surveillance data, comparing AVH incidence with AVH-associated mortality with an eye to population-based viral hepatitis control measures. Data presented here implicate HEV as the probable etiology of high mortality observed in pregnant women and in children less than 3 years of age in Uzbekistan during 1985-1987. High mortality among pregnant women but not among children less than 3 years has been observed in previous descriptions of epidemic hepatitis E. The high mortality among younger children observed in an AVH outbreak associated with hepatitis E merits corroboration in future outbreaks.

Dataset Information

IL28B polymorphisms and clinical implications for hepatitis C virus infection in Uzbekistan.

Aims

Methods

Results

Conclusions

Publications

IL28B polymorphisms and clinical implications for hepatitis C virus infection in Uzbekistan.

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