Cytokine and apoptosis gene polymorphisms influence the outcome of hepatitis C virus infection

BACKGROUND:Hepatitis C virus (HCV) infection is thought to be chronic and the factors leading to viral clearance or persistence are poorly understood.This study was undertaken to investigate the possibility of a significant relationship between the spontaneous clearance or the persistence of hepatitis C virus (HCV) infection and cytokine and apoptosis gene polymorphisms in Tunisian patients on hemodialysis.METHODS:Polymorphisms of the genes IL-1 (-889 IL-1α,-511 and +3954 IL-1β,IL-1Ra),IL-18 (-137 and-607),IL-12 (-1188) and Apo1/Fas (-670) were determined by PCR-RFLP,PCR-SSP and PCR-VNTR in 100 healthy blood donors and 100 patients infected with HCV and undergoing hemodialysis.The patients were classified into two groups:G1 consisted of 76 active chronic hepatitis patients (positive for HCV RNA) and G2 consisted of 24 hemodialysed patients who spontaneously eliminated the virus (negative for HCV RNA).RESULTS:The frequency of genotype association [-137GC/-607CA] IL-18 was higher in G2 (41.7%) than in G1 (15.8%) (P=0.008;OR=0.26;95% CI,0.10-0.73).We also found a higher frequency of the AA genotype of the Apo1/Fas gene in G2 (41.6%) than in G1 (17.5%) (P=0.026;OR=3.49;95% CI,1.13-10.69).Adjustment for known covariate factors (age,gender and genotype) confirmed these univariate findings and revealed that the genotype association GC-CA of the (-137 and-607) IL-18 gene and the AA genotype of the Apo1/Fas gene were associated with the clearance of HCV (P=0.041 and 0.017,respectively).CONCLUSION:The two genotypes GC-CA of the (-137 and-607) IL-18 polymorphism and the AA genotype of the Apo1/Fas gene influence the outcome of HCV infection in Tunisian patients on hemodialysis.

Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation:a single-center experience

Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation(allo-HSCT).We retrospectively analyzed specific polymorphisms in genes for interleukin(IL)-10,IL-6,tumor-necrosis factor alpha(TNF-α)and interferon gamma(IFN-c)in a pediatric cohort of 57 histocompatibility leucocyte antigen(HLA)-identical sibling myeloablative transplants.Both recipient and donor genotypes were tested for association with graft-versus-host disease(GVHD)by statistical methods including Cox regression analysis.We found a significant association between the IL-10 promoter haplotype polymorphisms at positions-1082,-819 and-592 with the occurrence of severe(grades Ⅲ–Ⅳ)acute GVHD(aGVHD).Recipients with the haplotype GCC had a statistically significant decreased risk of severe aGVHD(hazard risk(HR)50.20,95% confidence interval(CI):0.06–0.67)in comparison with patients with other IL-10 haplotypes(P50.008).Transplant-related mortality at 1 year was significantly lower in recipients with this haplotype(HR50.17,95% CI:0.012–0.320)versus other IL-10 haplotypes(P=0.03),whereas overall survival was not influenced by IL-10 haplotype polymorphisms.In multivariate analysis,the presence of the IL-10 GCC haplotype was found as the only variable associated with a statistically significant decreased hazard of severe aGVHD development(P=0.02,HR50.21,95% CI:0.05–0.78).These results suggest that pediatric patients possessing the IL-10 GCC haplotype may be protected from the occurrence of severe aGVHD in the setting of matched sibling HSCT.

IL-1β: an important cytokine associated with febrile seizures?

Febrile seizures （FSs） are the most common convulsions in childhood. Studies have demonstrated a significant relationship between a history of prolonged FSs during early childhood and temporal sclerosis, which is responsible for intractable mesial temporal lobe epilepsy. It has been shown that interleukin-1β （IL-1β） is intrinsically involved in the febrile response in children and in the generation of FSs. We summarize the gene polymorphisms, changes of IL-1β levels and the putative role of IL-1β in the generation of FSs. IL-1β could play a role either in enhancing or in reducing neural excitability. If the enhancing and reducing effects are balanced, an FS does not occur. When the enhancing effect plays the leading role, an FS is generated. A mild imbalance can cause simple FSs while a severe imbalance can cause complex FSs and febrile status epilepticus. Therefore, anti-IL-1β therapy may help to treat FSs.