Variations in the Nrampi gene and susceptibility to tuberculosis in West Africans
Variations in the Nrampi gene and susceptibility to tuberculosis in West Africans
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DOI：
10.1056/nejm199803053381002
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发表时间：
1998-03-05
影响因子：
158.5
通讯作者：
Hill, AVS
中科院分区：
文献类型：
--
作者：
Bellamy, R;Ruwende, C;Hill, AVS
背景 遗传因素可能影响结核病的易感性，但尚未发现控制易感性的特定基因。在小鼠中，对某些分枝杆菌感染的自然抵抗力受到自然抵抗相关巨噬细胞蛋白 1 (Nramp1) 基因的影响，但该基因的人类同源物 NRAMP1 在结核病中的作用尚不清楚。我们在冈比亚、西方的结核病病例对照研究中分型了 NRAMP1 的多态性 非洲方法使用序列特异性寡核苷酸杂交和微卫星分析对 410 名涂阳肺结核成人（平均年龄 34.7 岁）和 417 名种族匹配的健康对照者进行 NRAMP1 多态性分型。排除了人类免疫缺陷病毒感染的患者。 结果 四个 NRAMP1 多态性均与结核病显着相关，与最常见 NRAMP1 基因型的受试者相比，内含子 4 和基因 3' 非翻译区两个 NRAMP1 多态性杂合的受试者在结核病患者中的比例尤其过高（赔率 比率，4.07； 95% 置信区间，1.86 至 9.12；卡方=14.58；磷
Background Genetic factors may affect the susceptibility to tuberculosis, but no specific genes governing susceptibility have been identified. in mice, natural resistance to infection with some mycobacteria is influenced by the gene for natural-resistance-associated macrophage protein 1 (Nramp1), but the role of the human homologue of this gene, NRAMP1, in tuberculosis is unknown, We typed polymorphisms in NRAMP1 in a case-control study of tuberculosis in the Gambia, West Africa.Methods Sequence-specific oligonucleotide hybridization and microsatellite analysis were used to type NRAMP1 polymorphisms in 410 adults (mean age, 34.7 years) with smear-positive pulmonary tuberculosis and 417 ethnically matched, healthy controls. Patients with human immunodeficiency virus infection were excluded.Results Four NRAMP1 polymorphisms were each significantly associated with tuberculosis, Subjects who were heterozygous for two NRAMP1 polymorphisms in intron 4 and the 3' untranslated region of the gene were particularly overrepresented among those with tuberculosis, as compared with those with the most common NRAMP1 genotype (odds ratio, 4.07; 95-percent confidence interval, 1.86 to 9.12; chi-square=14.58; P