Abstract:
Pakistan is a low socio economic country having more than 10 million
people infected with hepatitis C Virus (HCV) with a major genotype of 3a (GT 3a).
Due to high rate of resistance to standard interferon plus ribavirin therapy, it is
highly needed to identify new marker for response prediction to therapy.
Interleukin 10 (IL-10) is a key member of cytokine, which regulates Th1/Th2
cytokine balance, a major part of immune system against infection. As IL-10
production varies interindividually based on some functional polymorphism in its
promoter region. We studied the impact of functionally important polymorphism (-
1082 G/A, -819 C/T and -592 C/A) on HCV infection susceptibility and on
outcomes of standard interferon plus ribavirin therapy. 90 healthy subjects and 140
HCV patients (95 were responder and 45 were non-responder to therapy) were
included in this study. Amplification refractory mutation system-polymerase chain
reaction (ARMS-PCR) method was used for IL-10 polymorphism genotyping.
High IL-10 producing -1082 GG genotype (p= 0.02; OR= 0.4; 95% CI= 0.2-0.8)
and GTA haplotype (p=0.03; OR= 0.55; 95% CI= 0.3-1) were significantly higher
in HCV patients as compared to healthy subjects. IL-10 -1082 GA genotype
(p=0.03; OR= 1.95; 95% CI= 1.1-3.4) showed protective effect against HCV
infection while other allelic, genotypic and haplotypic variants were nonsignificant
among HCV patients compared with healthy controls. The current data failed to
show any significant co relation between IL-10 polymorphism inheritance and
therapy response in HCV patients. Our data showed a significant effect of IL-10
promoter gene polymorphisms and HCV infection susceptibility or protection but
fail to demonstrate the influence of IL-10 promoter gene polymorphisms on the
response to combination therapy in Pakistani chronic hepatitis C patients infected
with 3a genotype. The impact of genetic variations in IL-10 polymorphic variants
on the response to anti-HCV treatment among different ethnic populations
deserves further examination.
