IL28B and IL10R −1087 polymorphisms are protective for chronic genotype 1 HCV infection and predictors of response to interferon-based therapy in an East-Central European cohort

BMC Research Notes

Béla Melegh⁸  Péter Kisfali⁸  László Szereday⁴  Áron Vincze^1,10  Zsolt Szinku⁷  Attila Haragh⁷  Béla Hunyady^1,10  Anna Tusnádi^1,12  Zoltán Péterfi^1,10  Zsuzsanna Nemes^1,10  János Schuller¹  Judit Gervain^1,11  Márta Varga²  János Fehér⁶  Gabriella Lengyel⁶  Mária Papp⁵  Edit Fráter⁵  Dalma Várszegi⁹  Ferenc Szalay³  István Tornai⁵  Gabriella Pár^1,10  Alajos Pár^1,10 

[1] United Szent István and Szent László Hospital, 1097 Budapest, Hungary;Réthy Pál Hospital, 5600 Békéscsaba, Hungary;First Department of Medicine, Semmelweis University, 1082 Budapest, Hungary;Department of Medical Microbiology and Immunology, University of Pécs, 7624 Pécs, Hungary;Second Department of Medicine, University of Debrecen, 4012 Debrecen, Hungary;Second Department of Medicine, Semmelweis University, 1088 Budapest, Hungary;Kaposi Mór Teaching Hospital, 7400 Kaposvár, Hungary;Department of Medical Genetics, University of Pécs, 7624 Pécs, Hungary;Department of Dermatology, University of Pécs, 7627 Pécs, Hungary;First Department of Medicine, University of Pécs, Rákóczi u. 2, 7623 Pécs, Hungary;Szent György Hospital, 8000 Székesfehérvár, Hungary;Hetényi Géza Hospital, 5004 Szolnok, Hungary

关键词: Interleukin-10;    Interleukin-28B;    Interferon;    Hepatitis C virus;    Genetic polymorphism;   

Others  :  1134944
DOI  :  10.1186/1756-0500-7-12

 received in 2013-09-12, accepted in 2014-01-03,  发布年份 2014

【 摘 要 】

Background

Previous studies have shown that single nucleotide polymorphisms (SNP) in IL28B and IL10R are associated with sustained virological response (SVR) in chronic hepatitis C patients treated with pegilated interferon plus ribavirin (P/R). The present study extends our earlier investigations on a large East-Central European cohort. The allele frequencies of IL28B and IL10R in genotype 1 HCV infection were compared with that of healthy controls for the purpose of examining the relationship between the polymorphisms and the SVR to P/R treatment.

Methods

A total of 748 chronic HCV1 infected patients (365 male, 383 female; 18–82 years) and 105 voluntary blood donors as controls were enrolled. Four hundred and twenty HCV patients were treated with P/R for 24–72 weeks, out of them 195 (46.4%) achieved SVR. The IL28 rs12979860 SNP was determined using Custom Taqman SNP Genotyping Assays. The IL10R −1087 (also known as IL10R −1082 (rs1800896) promoter region SNP was determined by RT-PCR and restriction fragment length polymorphism analysis.

Results

The IL28B CC genotype occurred with lower frequency in HCV patients than in controls (26.1% vs 51.4%, p<0.001). P/R treated patients with the IL28B CC genotype achieved higher SVR rate, as compared to patients with CT (58.6% vs 40.8%, p=0.002). The prevalence of IL10R −1087 GG genotype was lower in patients than in controls (31.8 % vs 52.2%, p<0.001). Among patients achieving SVR, the IL10R −1087 GG genotype occurred with higher frequency than the AA (32.0% vs 17.4%, p=0.013). The IL28B T allele plus IL10R A allele combination was found with higher prevalence in patients than in controls (52% vs 20.7%, p<0.001). The IL28B CC plus IL10R A allele combination occurred with higher frequency among patients with SVR than in non-responders (21.3% vs 12.8%, p=0.026). Both the IL28B CC plus IL10R GG and the IL28B CC plus IL10R A allele combinations occurred with lower frequency in patients than in controls.

Conclusions

In our HCV1 patients, both the IL28B CC and IL10R GG genotypes are associated with clearance of HCV. Moreover, distinct IL28B and IL10R allele combinations appear to be protective against chronic HCV1 infection and predictors of response to P/R therapy.

【 授权许可】

   
2014 Pár et al.; licensee BioMed Central Ltd.

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