| Background:Tuberculosis is caused by mycobacterium tuberculosis (MT). Tuberculosis appeared recrudescence in global in recent 20 years. The rate of tuberculosis infection is 33.3% in world wide, but 44.5% in our country. China ranked second in the world in the number of TB patients, and is one of 22 TB countries high-burden in the world. Children are susceptible to tuberculosis. Recent 5 years, hospitalized patients with tuberculosis increased obviously in Chongqing children's hospital.As the infect rate of tuberculosis in monozygotic twins at the same time is higher than in dizygotic twins and is different in different race of people, so that the variance of host genetic background influences the susceptibility and resistance to tuberculosis. Single nucleotide polymorphisms (SNP) is the third generation of genetic marker which reflects the genetic diversity among race, crowd and individual truly. There are many important significant to research the relationship between SNP and diseases for investigating the genetic background of diseases and exploring new ways to prevent and cure diseases. Cell immunity, especially TH1 cells mediated immune response play an important role in tuberculosis infection. IFN-γand its inducing factors, i.e. IL-12 and IL-18, are thought being the chief cytokines to immune defence of tuberculosis infection. IL-18 is a newer IFN-γinducer and can trigger NK and TH1 cells secreting IFN-γ, promote the proliferation and cytotoxic activity of TH1 cells and NK cells.IL-18 polymorphisms influence the expression and secretion of itself. There are two SNPs in IL-18 gene promoter region at -137 and -607 sites. They are predicted as nuclear factor binding sites of H4TF-1 and cAMP- responsive element binding protein, respectively. The mutation of the two sites can not only influence the expression of IL-18 and also potentially expression of IFN-γand TH1 cell immune function. IL-18 needs combine with its receptor composed ofαandβchains to paly biological effection. Thus, the level of IL-18 receptor also will influence the the level of IFN-γand the effection of anti-tuberculosis infection. Upto now, there is not report about the relationship of IL-18 and its receptor gene promoter region polymorphisms with tuberculosis susceptibility.Objective:To analyze clinical feature and auxiliary examination of children tuberculosis in Chongqing. To analyze the difference of genotypic frequencies between Chongqing tuberculosis patients and healthy people in IL-18 (the position -137G/C and -607C/A), IL-18Rα(the position -69C/T and -638C/T) gene promoter single nucleotide polymorphisms (SNP), to reveal influence of polymorphisms to tuberculosis susceptibility.Methods:To detection gene polymorphisms of IL-18 and its receptor. Samples included 91 tuberculosis children and 32 tuberculosis adults, 167 normal children and 82 normal adults. Gene polymorphisms were analysed by PCR-SSP.Results:1,The ratio of cerebral tuberculosis in Chongqing children who exposed to tuberculosis is higher than who did not (P<0.05).2,The morbidity of cerebral tuberculosis who did not vaccinate BCG is higher than who did.3,The positive frequency of PPD test in acid-fast bacilli positive was higher than acid-fast bacilli negative (P<0.05).4,IL-18 gene polymorphisms at -137 site: The frequency of IL-18-137GG genotype in children tuberculosis groups of Chongqing was significantly higher than that in normal controls (P<0.05),the frequencies of GC and CC genotypes were not significantly different between children tuberculosis and normal controls (P>0.05). Allele C at position -137 in the promoter of IL-18 gene was significantly lower in children patients with tuberculosis than that in children controls (P<0.05). There was not different of genetypes and alleles at position -137 between adult tuberculosis and adult controls. The frequency of -137GG genotype in total tuberculosis groups was significantly higher than that in total normal controls (P<0.05), the frequencies of GC and CC genotypes were not significantly difference between total tuberculosis and total normal controls. Allele C at -137 was significantly lower in total patients with tuberculosis than that in controls (P<0.05).5,IL-18 gene polymorphisms at -607 site: The frequencies of all genotypes or alleles at IL-18 -607 distribution were not significant different in tuberculosis and normal controls.6,IL-18Rαgene polymorphisms at -69 site: The frequency of IL-18Rα-69 CC genotype in children tuberculosis was significantly lower than that in normal controls (P<0.01),the frequencies of CT and TT genotypes were not significantly difference between children tuberculosis and normal controls. Allele C at -69 was of a significantly lower frequency in children tuberculosis than that in normal controls (P<0.01). There were not difference of genetypes and alleles at position -69 between adult tuberculosis and adult controls. The frequency of -69CC genotype in total tuberculosis groups (children + adult) was significantly lower than that in normal controls (P<0.01). The frequencies of -69CT and -69TT genotypes were not significant difference between total tuberculosis and normal controls. Allele C at -69 was of a significantly lower frequency in total tuberculosis than that in normal controls (P<0.01). And there was significant difference of alleles at -69 among pulmonary tuberculosis, out of pulmonary tuberculosis and pulmonary tuberculosis plus out of pulmonary tuberculosis (P<0.01).7,IL-18Rαgene polymorphisms at -638 site: The frequencies of all genotypes or alleles at IL-18Rα-638 distribution were not significant difference in tuberculosis and normal controls. But allele C at -638 in cerebral tuberculosis children was significantly lower than that in other tuberculosis children, and allele C in severe tuberculosis children lower than that in common tuberculosis children (P<0.01).Conclusion:1,To prevent children tuberculosis especially cerebral tuberculosis one of the most important questions is refraining from children exposure to tuberculosis and BCG vaccination suscessfully.2,In Chongqing children tuberculosis the positive frequency of PPD test in bacilli positive was higher than bacilli negative (P<0.05).3,Position -137 of IL-18 gene polymorphisms relates with tuberculosis susceptibility of Chongqing people. Allele G is a possible predisposing genes of tuberculosis, allele C maybe plays a role in preventing mycobacterium tuberculosis infection. But -607 site of IL-18 gene polymorphisms is not related with tuberculosis in Chongqing possibly.4,Position -69 of IL-18Rαallele T is possible predisposing genes of tuberculosis. Allele C may play a role in preventing mycobacterium tuberculosis infection. Alleles of position -69 possibly play a special role in multiple tuberculosis. But -638 site of IL-18Rαgene polymorphisms is not related with tuberclosis of Chongqing possibly. But allele C relates with severity of tuberculosis possibly.
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