| Background and Objective:Tuberculosis is caused by mycobacterium tuberculosis(MTB). Tuberculosis appears to 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 the second in the world in the number of TB patients, and is one of 22 countries of TB high-burden in the world. It has been estimated that One third of the world's population is infected by Mycobacterium tuberculosis but only about 5%-10% of the infected people will develop clinical disease in their life time. Many factors affect TB development, such as alcohol, malnutrition, and human immunodeficiency virus (HIV) infection. As the evidences from the different concordance rates in monozygotic and dizygotic twins and the racial difference in susceptibility to M.tuberculosis suggesting that the variance of host genetic background influence the susceptibility and resistance to tuberculosis.Cell-mediated immune response of host is an important component of tuberculosis immunity. It is a complicated immunologic process mediated by the T cell ,in which the mononuclear and macrophage participate. Upon infection, phagocytes are activated to produce a series of cytokines,which participate in immuno-regulation of tuberculosis. Polymorphisms in the cytokine genes are known to influence cytokine levels and may be associated with outcome of infections. Candidate gene approach and association studies have identified various host genetic factors that affect susceptibility to TB. Unraveling the mechanisms underlying the genetic variations that influence susceptibility to TB may lead towards better understanding of the pathogenesis of TB and development of prophylactic or treatment strategies.IFN-γand IL-10 are considered to be the most important cytokines ,which implicate in the pathogenesis of tuberculosis. The polymorphisms of IFN-γand IL-10 genes have been shown to be associated with the susceptibility to the development of tuberculosis in other populations. Up to now, there have been not correlative reports in Han population. Based on the studies abroad ,the aim of the present work was to investigate whether the polymorphisms of IFN-γ+874T/A and IL-10-1082G/A genes were associated with the susceptibility to the development of pulmonary tuberculosis or not in Guangdong Han population. The results of the study may be considered genetic markers to be used to early identify individuals at high risk of PTB, which may play an important role for preventing the development of TB in clinical practice.Methods and Materials1.Subjects: In our study ,the group of IFN-γwas composed of 60 patients with PTB and 60 patients with heathy control group; 40 patients with PTB and 40 patients with heathy control group were enrolled in the IL-10 group. There were no genetic relationship between the subjects of the two groups. Randomly selected controls were matched to the patients by age and gender.2.The target region of IFN-γ(+874) and IL-10(-1082) gene were amplified with the primers designed according to the reference. The SNPs in the first intron +874T/A of IFN-γgene and in promoter of IL-10 gene at position-1082 were detected with PCR-SSP. The genotypes and alleles frequencies were calculated and analyzed.Results1. All the genotypes of IFN-γ(+874 T/A)and IL-10(-1082G/A) polymorphisms in the patients group and the controls one were analyzed by Hardy-Weinberg equilibrium test, which showed that there were genetic equilibriums (all P values>0.05), suggesting that the subjects possessed representativeness of Guangdong Han population. 2. Association of the polymorphism in the first intron of interferon-γgene with susceptibility to the pulmonary tuberculosis.The characteristics of the genotypic and the allele frequencies: A highly significant difference in the distribution of IFN-γgene polymorphism at position+874 was observed between the patients group(AA,AT and TT frequencies were 80%,16.7%and3.3%, respectively)and the control one(53.3%,33.3% and 13.3%,respectively),in which the genotypic frequency of AA in the patients group was higher significantly than that in the control group(x2=9.6,P=0.002), the genotypic frequencies of AT and TT in the patient group were significantly lower than those in the control group(x2=4.444,P=0.035;x2=3.927,P=0.048).The A allele frequency of IFN-γgene in the patients group was statistically higher compared with that in the control group(x2=12.227,P=0.000),in which the Odds risk rate(OR) was 3.245,95%CI 1.643～6.408.3. Association of the-1082G/A polymorphisms in promoter of IL-10 gene with susceptibility to the pulmonary tuberculosis.The characteristics of the genotypic and the allele frequencies: The difference in the distribution of IL-10 gene polymorphism at position- 1082 was observed between the patients group(AA,GA and GG frequencies were 55%,40% and 5%, respectively)and the control group(82.5%,15% and 2.5%,respectively).The genotypic frequency of AA in the control group was higher than that in the patients group(x2=7.040,P=0.008), in contrast with which the genotypic frequency of GA in the patient group was higher than that in the control group(x2=6.270,P=0.012)and no statisticant difference[0] was found in the genotypic frequency of GG between the two groups(x2=0.346,P=0.556). The G allele frequency of IL-10 gene in the patients group was statistically higher compared with that in the control group (x2=6.234,P=0.013),in which the Odds risk rate(OR) was 3, 95%CI 1.234～6.295.Conclusions:1. The frequencies of A allele and AA genotype in the first intron of IFN-γ(+874T/A) gene may be important genetic risk markers for the development of active pulmonary tuberculosis in the Guangdong Han population. 2.The frequencies of G allele and the GA genotype in the promoter of IL-10(-1082G/A) gene may be important genetic risk markers for the development of active pulmonary tuberculosis in the Guangdong Han population.3.IFN-γand IL-10 genes may be the candidate genes of the susceptibility to pulmonary tuberculosis for the Guangdong Han population.
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