title: IFNG polymorphisms are associated with tuberculosis in Han Chinese pediatric female population.
abstract: Host genetic factors play a major role in determining differential susceptibility to human tuberculosis (TB), a re-emerging infectious disease throughout the world. Genetic variations in the IFNG gene coding for interferon gamma (IFN-γ), have been identified in TB patients. To investigate the association of the IFNG polymorphisms with TB susceptibility in Chinese pediatric population. A case-control study of 189 TB patients and 164 controls was performed using single-nucleotide polymorphism (SNP) analysis. Genomic DNA was extracted from leukocytes in peripheral blood. Three SNPs of IFNG, including -1616C/T (rs2069705), +874A/T (rs2430561), and +3234C/T (rs2069718), were selected for genotyping and analysis. The +874A and +3234C alleles were more frequent among TB patients (P = 0.108 and P = 0.088), especially in females (both P = 0.029), although this difference was not significant since Bonferroni corrected significance threshold was 0.025 (two of three SNPs were found to be in linkage disequilibrium). More pronounced differences for the +874 and +3234 polymorphisms were found under the genotype comparison between TB cases and controls in the total population [P = 0.026 (borderline non-significance) and P = 0.020, respectively], and in the female subgroup (P = 0.020 and P = 0.020). The dominant model of inheritance was shown to be significant for +874A and +3234C alleles (both P = 0.019) in the female subgroup. The +874A and +3234C alleles were more frequently found in extrapulmonary TB patients than in controls (P = 0.039). Haplotype analysis carried out on these three SNPs showed the TTT haplotype to be more frequent in controls than in TB cases, and this difference showed a strong significance (P = 0.005). The +874A and +3234C alleles may be related to TB susceptibility in the female subgroup in the Chinese pediatric population of North China. The higher rate of +874A (known to correlate with lower IFN-γ expression) in the extrapulmonary TB subgroup suggests a sufficient IFN-γ expression to be not only an important factor for the onset of TB disease but also for limiting its dissemination to lungs.
authors.affiliation: Key Laboratory of Major Diseases in Children and National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital Affiliated to Capital Medical University, No. 56 Nan-li-shi Road, Xicheng District, Beijing, 100045, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shen
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Jiao
authors.forename: Wei-Xing
authors.initials: WX
authors.lastname: Feng
authors.forename: Xi-Rong
authors.initials: XR
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.forename: Qing
authors.initials: Q
authors.lastname: Miao
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Shen
authors.forename: A-Dong
authors.initials: AD
authors.lastname: Shen
mesh_terms: D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D017931:DNA Primers / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics*; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014376:Tuberculosis / Q000235:genetics*
chemical_list: D017931:DNA Primers; C573415:IFNG protein, human; D007371:Interferon-gamma