Jin Jing, Sun Lin, Jiao Weiwei, Zhao Shunying, Li Huimin, Guan Xiaolei, Jiao Anxia, Jiang Zaifang, Shen Adong
Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Clin Infect Dis. 2009 Mar 15;48(6):733-8. doi: 10.1086/597034.
Tuberculosis is an urgent public health problem caused by Mycobacterium tuberculosis infection. Many factors, including host genetic factors, are involved in tuberculosis pathogenesis. The SLC11A1 gene (formerly NRAMP1) is a primary candidate for association with tuberculosis susceptibility.
We examined the association between SLC11A1 polymorphisms and susceptibility to tuberculosis in Han Chinese children. The study included 136 pediatric patients with tuberculosis and 435 pediatric control subjects. Polymerase chain reaction restriction fragment-length polymorphism analysis was performed with blood samples to distinguish allele genotypes of INT4 (a G-->C single nucleotide change in intron 4, 469 + 14G/C) and the 3'UTR (TGTG deletion in the 3' untranslated region, 1729 + 55del) in the SLC11A1 gene. Differences in genotype frequency were analyzed for patients with tuberculosis and control subjects.
We did not identify any statistically significant differences between the tuberculosis and control groups with regard to the frequency of genotype variants G/C and C/C at the INT4 locus. The frequency of genotype variants (TGTG +/delete and TGTG delete/delete) was significantly higher in the tuberculosis group than in the control group at the 3'UTR locus. Differences in genotype distribution at the 3'UTR locus were only identified in female subjects, with a greater number of variant genotypes in the tuberculosis group.
Variant genotypes at the 3'UTR locus in the SLC11A1 gene were associated with pediatric tuberculosis in Chinese patients. Patient sex may affect the outcome of M. tuberculosis infection in children.
结核病是由结核分枝杆菌感染引起的一个紧迫的公共卫生问题。包括宿主遗传因素在内的许多因素都参与了结核病的发病机制。溶质载体家族11成员A1基因(以前称为天然抗性相关巨噬细胞蛋白1基因)是与结核病易感性相关的主要候选基因。
我们研究了汉族儿童溶质载体家族11成员A1基因多态性与结核病易感性之间的关联。该研究纳入了136例患结核病的儿科患者和435例儿科对照受试者。对血样进行聚合酶链反应-限制性片段长度多态性分析,以区分溶质载体家族11成员A1基因中内含子4(第469+14位碱基处的G→C单核苷酸变化,INT4)和3'非翻译区(3'非翻译区的TGTG缺失,1729+55del)的等位基因基因型。分析了结核病患者和对照受试者的基因型频率差异。
我们未发现结核病组和对照组在INT4位点的基因型变体G/C和C/C频率上有任何统计学显著差异。在3'非翻译区位点,结核病组的基因型变体(TGTG+/缺失和TGTG缺失/缺失)频率显著高于对照组。仅在女性受试者中发现了3'非翻译区位点的基因型分布差异,结核病组的变异基因型数量更多。
溶质载体家族11成员A1基因3'非翻译区位点的变异基因型与中国患者的儿童结核病相关。患者性别可能影响儿童结核分枝杆菌感染结局。