The impact of IL-6 and IL-28B gene polymorphisms on treatment outcome of chronic hepatitis C infection among intravenous drug users in Croatia.
BACKGROUND
Several genes and their single nucleotide polymorphisms (SNPs) are associated with either spontaneous resolution of hepatitis C infection or better treatment-induced viral clearance. We tested a cohort of intravenous drug users (IVDU) diagnosed with chronic hepatitis C virus (HCV) for treatment response and its association with the SNPs in the interleukin-6 (rs1800795-IL6) and the interleukin-28B (rs12979860-IL28B) genes.


METHODS
The study included 110 Croatian IVDU positive for anti-HCV antibody. Genotyping was performed by polymerase chain reaction (PCR) based approach. Patients were treated by standard pegylated-interferon/ribavirin and followed throughout a period of four years, during which sustained virological response (SVR) was determined. All data were analysed with statistical package SPSS 19.0 (IBM Corp, Armonk, NY, USA) and PLINK v1.07 software.


RESULTS
Patients showed a significantly better response to treatment according to the number of copies of the C allele carried at rs1800795-IL6 (P = 0.034). All but one of the patients with CC genotype achieved SVR (93%), whereas the response rate of patients with GG genotype was 64%. The association of rs1800795-IL6 with SVR status remained significant after further adjustment for patients' age, fibrosis staging, and viral genotype (OR 2.15, 95% CI 1.16-4.68, P = 0.019). Distributions of allele frequencies at the locus rs12979860-IL28B among the study cohort and the underlying general population were suggestive of a protective effect of CC genotype in acquiring chronic hepatitis C in the Croatian IVDU population.


CONCLUSIONS
The rs1800795-IL6 polymorphism is associated with positive response to treatment in IVDU patients positive for HCV infection. A protective role of rs12979860-IL28B CC genotype in acquiring chronic hepatitis C is suggested for Croatian IVDU population.
Department of Internal Medicine, Division of Gastroenterology, Clinical Hospital Split, Split, Croatia.
Zoran
Z
Bogdanović
Department of Immunology, Univeristy of Split, School of Medicine, Split, Croatia.
Ivana
I
Marinović-Terzić
Department of Pathology, Clinical Hospital Split, Split, Croatia.
Sendi
S
Kuret
Department of Research in Biomedicine and Health, Univeristy of Split, School of Medicine, Split, Croatia.
Ana
A
Jerončić
Department of Infectious Diseases, Clinical Hospital Split, Split, Croatia.
Nikola
N
Bradarić
Department of Pathology, Clinical Hospital Split, Split, Croatia.
Gea
G
Forempoher
Department of Public Health, Univeristy of Split, School of Medicine, Split, Croatia.
Ozren
O
Polašek
Department of Pathology, Clinical Hospital Split, Split, Croatia.
Šimun
Š
Anđelinović
Department of Immunology, Univeristy of Split, School of Medicine, Split, Croatia.
Janoš
J
Terzić
Genetic variation; Hepatitis C; IL-28; IL-6; Intravenous drug users; Sustained virological response