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  • 1 I-st Department of Medicine, Pécs, Hungary
  • 2 Department of Medical Genetics, University of Pécs, Pécs, Hungary
  • 3 II-nd Department of Medicine, University of Debrecen, Debrecen, Hungary
  • 4 St. György Hospital, Székesfehérvár, Hungary
  • 5 I-st Department of Medicine, Semmelweis University, Budapest, Hungary
  • 6 Réthy Pál Hospital, Békéscsaba, Hungary
  • 7 United St. István and St. László Hospital, Budapest, Hungary
  • 8 Hetényi Géza Hospital, Szolnok, Hungary
  • 9 II-nd Department of Medicine, Semmelweis University, Budapest, Hungary
  • 10 First Department of Medicine, University of Pécs, Ifjúság u. 13, H-7624 Pécs, Hungary
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Abstract

Background

Since the clearance of hepatitis C virus (HCV) infection depends on the cytokines which are under genetic control, we have studied genetic polymorphisms of two pro-inflammatory interleukin-28B (IL-28B) (also named as interferon λ-3) and lymphotoxin-A (LT-A) as well as of one anti-inflammatory cytokine interleukin-10 (IL-10) genes in patients with HCV infection. We examined the allele frequencies of these genes in HCV patients as compared with healthy controls, and determined their association with sustained virological response (SVR) on PEG-IFN α-2a + ribavirin (RBV) (P/R) treatment, to assess the predictive value of these genetic variants. A total of 292 chronic HCV genotype 1 infected patients and 104 healthy controls have been studied. The samples were genotyped using PCR-RFLP and ABI Taqman genotyping assay.

Results

IL-28B — The C/C genotype in HCV patients occurred with lower frequency than in healthy controls (28.11% vs. 51.92%, p = 0.0001, OD 2.76), suggesting a protective role of this variant. At the same time, P/R treated patients with this C/C genotype achieved SVR at a higher rate, than those who have TT genotype (54.34% vs. 29.16%, p = 0.0447, OD 2.86). LT-A A252G — The frequency of A/A genotype did not differ between HCV patients and controls, but G/G homozygosity was found at a reduced rate in non-treated subgroup of HCV patients as compared to controls (2.91% vs. 9.90%, p = 0.041, OR 3.66). The G/G genotype seemed to be a predictor of SVR versus A/A genotype: SVR occurred in G/G pts 54.54% versus 44.94% in AA cases (not significant, NS). IL-10R 1087 — The G/G genotype in HCV patients occurred with lower frequency than in controls (37.15% vs. 52.74%, p = 0.00957, OD 1.89). G/G harboring patients showed higher SVR than patients with A/A genotypes (41.26% vs. 28.57%) (NS).

Conclusion

We have found that IL-28B C/C genotype was a protective genetic variant and a predictor of SVR in chronic HCV infection. Furthermore, our data suggest that presumable predictors may also be both IL-10 and LT-A gene polymorphisms; however, that needs to be confirmed by studies with a larger number of HCV patients.

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