| Pulmonary tuberculosis is a chronic infectious lung disease caused by infection with Mycobacterium tuberculosis.Although the control of TB has been implemented around the world for many years,there are still a large number of new cases and deaths every year.In China,TB has already become a severe public health problem and brung heavy disease burden to population.However,not all people infected with MTB will become sick,most of infected people are latent infection and the result of infection depends on the host’s immune state.IL-23 play an important role as a link between innate and adaptive immunity.Lack of IL-23 R might directly affect the body’s immune response to MTB and genetic factors have close relationship with immune state.Recently,despite IL-23 R polymorphisms were found to have association with a number of diseases,the relationship between SNPs of IL-23 R and TB was relatively unexplored.Therefore,the study on relationship between IL-23 R gene polymorphisms and PTB is crucial to control TB and understand the genetic mechanism of TB comprehensive.Objective:To investigate interleukin-23 receptor(IL-23R)polymorphisms for susceptibility to pulmonary tuberculosis.Methods:A case-control study was performed,a total of 243 pulmonary tuberculosis(PTB)cases were selected from Beijing chest Hospital,Capital Medical University during March 2014 to December 2015 and 226 healthy controls were recruited by the tuberculosis physical examination in Beijing Changping center for tuberculosis control and prevention during May 2014 to October 2014.Nine polymorphic sites(rs3762318,rs11209026,rs10889657,rs10889677,rs6682925,rs1004819,rs11465804,rs2201841,rs7514847)were screened out by using Haploview software from Hapmap database,single nucleotide polymorphisms(SNPs)were detected by ligase detection reaction(LDR)for genotyping and frequency comparison,linkage analysis and haplotype analysis were performed to find out linkage disequilibrium and haplotype.Through above-mentioned methods,the association between SNPs and PTB were estimated.Results:There was a significant difference in the distribution of IL-23 R gene polymorphism at polymorphic site rs6682925 between PTB cases and healthy controls,allele C frequency in cases 44.0%(213/484)is significantly higher than in controls(37.4%(169/452),χ2 =4.24,P=0.040,OR= 1.32(95%CI=1.07-1.71),genotype TT frequency in cases(30.1%(73/242)was significantly higher than in controls 38.9%(88/226),χ2 =3.99,P<0.05,OR=0.68(95%CI=0.46-0.99).The Polymorphic site rs3762318,allele T frequency in cases 16.0%(78/486)was significantly higher than in controls10.2%(46/450),χ2 =7.04,P<0.01,OR = 1.69(95%CI = 1.14-2.49);Genotype CC frequency in cases 3.3%(8/243)was significantly higher than in controls 0.4%(1/225),χ2 =5.02,P<0.05,OR=7.63(95%CI =0.95-61.46);Genotype TT frequency in cases 71.5%(173/243)was significantly higher than in controls 80.0%(180/225),χ2=4.89,P<0.05,OR=0.62(95%CI =0.40-0.95).Haplotype C G C T A C T C T build by nine target SNPs sites was found which distribute significant different in cases and controls by haplotype analysis,frequency in cases 5.1% was higher than in controls 2.2%,χ2 =5.65,P<0.05,OR=2.44(95%CI=1.14-5.19).A haplotype Block(rs3762318,rs10889657,rs6682925)was built,then we found haplotype T T T distribute significant different between the two groups,frequency in cases 55.7% was lower than in control s 61.3%,[χ2 =4.38,P =0.036;OR(95%CI):0.75(0.58-0.98)] Conclusion:Polymorphic sites rs6682925 and rs3762318 are widely existed among Chinese Han population and these two SNPs are susceptible to pulmonary tuberculosis.Haplotype C G C T A C T C T build by the TagSNPs sites is a risk factor for susceptibility to pulmonary tuberculosis,halotype T T T in Block is a protective factor for susceptibility to pulmonary tuberculosis in Chinese Han population. |
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