| Background:Acting as messenger molecule among immune cells, cytokines play a central role in innate and adaptive immunity. There are two kinds of cytokines, Thl secreting cytokines and Th2 secreting cytokines. The Thl cytokines, such as TNF-α, IL-2 and IFN-γ, are related to inducing celluar immunity and delay type hypersensitivity (DTH), resulting in anti intracellular pathogen infection and inflammatory reaction. Th2 cytokines, such as IL-4, IL-5 and IL-10, involved in humoral immunity, which play a key role in anti extracelluar pathogens, parasites and allergy. The cytokines work tightly controlled as network, and some polymorphisms of cytokine genes may affect cytokine expression and function. Previous studies have suggested that some polymorphisms of cytokine genes were associated with some autoimmune diseases, chronic virus infection, as well as vaccine-induced immunity.The genetic factors play important roles in the immune response to the vaccines. The antibody in different individuals showed extremely diverse even to the same vaccine. However, the present studies are focused on the vaccines which could not induce enough immune response after vaccine administration such as HBV, mealses vaccine, and smallpox vaccine. For the traditional inactivated vaccine with good immunogenicity, the genetic factors have always been ignored. Therefore, in present study, association study between some SNPs in cytokine genes and the humoral immunity following by inactivated Japanese encephalitis vaccine (JEV) vaccination has been invesitigated.Moreover, the association between cytokine genes and virus infection has also been proved. For example, after hepatitis C virus (HCV) infection, nealry 80% of individuals would develop into chronic infection. During the infection progress, the host native immunity, innate immunity, and adaptive immunity may play an important role in the elimination of the virus. And Th1 cytokines, TNF-α, IL-2, IFN-γ, which mainly mediate cellular immune response, showed more important in the elimination of HCV. Thus, the association between the gene polymorphisms of Thl cytokines, TNF-α, IL-2 and HCV chronic infection were analyzed in present study to provide basic data for clinic diagnosis and therapies of HCV infection.Method:(1).525 individuals who have administrated inactivated Japanese encephalitis vaccine (vero cell), were enrolled.18 SNPs of cytokines genes including SNP rs 1800629 (-308, G/A), rs3093668 (G/C) and rs3093726 (T/C) in TNF-a, SNP rs11932411 (A/G), rs11575812 (A/G), rs2069762 (-330, A/C), rs2069763 (-34, T/G), and rs4833248 (-2811, A/G) in IL-2, SNP rs2243247 (-1138,G/A), rs2243248 (-1100, A/C), rs2243250 (-590, T/C), rs2070874 (-33, C/T), rs2227284(2979, T/G), rs2243291(C/G), and rs2243292 (A/G) in IL-4, SNP rs1800896 (-1082, A/G), rs1800871 (-819, T/C) and rs1800872 (-592, A/C) in IL-10, were genotyped by real-time TaqMan polymerase chain reaction. Haplotypes of different cytokine genes were constructed, and the association of cytokine gene polymorphisms and Japanese encephalitis inactivated vaccine induced anitibody response were evaluated at both allele and haplotype levels.(2).380 HCV chronic infectious patients and 367 healthy individuals in Yunnan province were recruited. SNP rs1800629 (-308, G/A), rs3093668 (G/C) and rs3093726 (T/C) in TNF-a, SNP rs11575812 (A/G), rs2069762 (-330, A/C), rs2069763 (-34, T/G), and rs4833248 (-2811, A/G) in IL-2 were genotyped by real-time TaqMan polymerase chain reaction.The association of cytokine gene polymorphisms and HCV chronic infection were evaluated.Result:(1). In the JEV immune response association study, rs11932411 (A/G) in IL-2, rs2243247 (-1138, G/A), rs2243292 (A/G) in IL-4 showed no polymorphisms in present study population. Rs1800896 (-1082, A/G) GG genotype in IL-10 was associated with higher GMT of JEV neutralizing antibody (P<0.05). The further subgroup analysis, showed that rs1800629 (-308, G/A) genotype AG genotype in TNF-a was associated with lower GMT as well as lower seroconversion compared with AA+AG genotype in 1-6 years old group (P<0.05), while rs2227284 (2979, T/G) TG genotypes in IL-4 were associated lower GMT compared with homogenous genotype in 7-12 years old group (P<0.05). When the male and female group were divided, rs11575812 (A/G) A allele in IL-2 showed a lower JEV neutralizing antibody seroconversion compared with G allele in female (P<0.05), while rs2227284 (2979, T/G) TG genotype in IL-4 showed a lower GMT compared with homogenous genotypes in female (P<0.05).(2). In the study of HCV chronic infection, the frequency of rs2069762 (-330, A/C) CC genotype in IL-2 was higher in case group than in control group with the frequency of 0.161 vs 0.101 (P<0.05), rs2069763 (-34, T/G) G allele showed a higher frequency in case than that in control group (0.563 vs 0.511, P<0.05), the AATG haplotype constructed by rs11575812-rs2069762-rs2069763-rs4833248 in IL-2 demonstrated a lower frequency in case compared with that in control (P<0.05). Rs11575812 (A/G), rs4833248 (-2811, A/G) in IL-2, and rs1800629 (-308, G/A), rs3093668 (G/C) and rs3093726 (T/C) in TNF-a showed no association with HCV chronic infection.Conclusion:(1). The SNP rs1800896 in IL-10 was associated with the humoral inmmune response induced by inactivated Japanese encephalitis vaccine. The rs1800629 in TNF-a, rs11575812 in IL-2 and rs2227284 in IL-4 were associated with the humoral immune response induced by inactivated JEV at age or gender levels.(2). The SNP rs2069762 CC genotype and rs2069763 G allele may increase the risk of HCV chronic infection. In contrast, the AATG haplotype constructed by rs11575812-rs2069762-rs2069763-rs4833248 may be a protective factor to HCV chronic infection. |
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