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.
Mol Biol Rep. 2013 Sep;40(9):5477-82. doi: 10.1007/s11033-013-2647-7. Epub 2013 Jun 5.
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.
宿主遗传因素在决定人类结核病（TB）的易感性方面起着重要作用，结核病是一种在全球范围内重新出现的传染病。IFNG 基因编码的干扰素γ（IFN-γ）的基因变异已在结核病患者中被发现。为了研究中国儿科人群中 IFNG 多态性与结核病易感性的关系，我们进行了一项病例对照研究，纳入了 189 例结核病患者和 164 例对照。采用单核苷酸多态性（SNP）分析方法，从外周血白细胞中提取基因组 DNA。选择 IFNG 的三个 SNP 进行基因分型和分析，包括 -1616C/T（rs2069705）、+874A/T（rs2430561）和+3234C/T（rs2069718）。+874A 和 +3234C 等位基因在结核病患者中更为常见（P=0.108 和 P=0.088），尤其是在女性中（均为 P=0.029），尽管这种差异并不显著，因为 Bonferroni 校正的显著性阈值为 0.025（三个 SNP 中有两个被发现处于连锁不平衡状态）。在总人群中，结核病病例和对照组之间的基因型比较显示，+874 和 +3234 多态性的差异更为明显[P=0.026（边缘非显著性）和 P=0.020]，在女性亚组中更为明显（P=0.020 和 P=0.020）。在女性亚组中，显性遗传模型显示+874A 和 +3234C 等位基因具有显著性（均为 P=0.019）。+874A 和 +3234C 等位基因在外周性结核病患者中比对照组更为常见（P=0.039）。对这三个 SNP 进行的单体型分析显示，TTT 单体型在对照组中比结核病病例中更为常见，这种差异具有很强的显著性（P=0.005）。+874A 和 +3234C 等位基因可能与中国北方儿科人群中女性亚组的结核病易感性有关。在外周性结核病亚组中，+874A （已知与 IFN-γ表达降低相关）的发生率较高，表明 IFN-γ的表达不仅是结核病发病的一个重要因素，也是限制其向肺部传播的一个重要因素。
