Investigation of chromosome 17 candidate genes in susceptibility to TB in a South African population
Investigation of chromosome 17 candidate genes in susceptibility to TB in a South African population
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DOI：
10.1016/j.tube.2008.10.001
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发表时间：
2009-03-01
期刊：
影响因子：
3.2
通讯作者：
Hoal, Eileen G.
中科院分区：
文献类型：
--
作者：
Moeller, Marlo;Nebel, Almut;Hoal, Eileen G.
已知17号染色体含有结核病易感基因。这些基因中的两个，即NOS 2A和CCL 2的多态性与各种人群中的TB相关。为了研究南非有色人种中基因变异与结核病的可能关联，我们对800多例结核病病例和对照组中NOS 2A和CCL 2的SNP进行了基因分型。我们发现结核病与NOS 2A启动子中含有功能性rs 9282799和rs 8078340 SNP的两种单倍型之间存在显著关联。rs 8078340的T等位基因，在病例中过度代表的单倍型中发现（p = 0.015，pc = 0.038，OR = 1.4，95% CI [1.1 - 1.8]），先前显示减少结合的DNA-蛋白质复合物的量以及结合的持续时间，并可能减少一氧化氮（NO）的产生。rs 8078340的C等位基因存在于对照组中更常见的单倍型中（p = 0.011，pc = 0.029，OR = 1.4，95% CI [1.1 - 1.8]）。在NOS 2A的单点分析中，rs 2779249（以前与结核病相关;在巴西人中）和功能性rs 8078340名义上与疾病相关。在所研究的任何其他SNP或单倍型与TB之间未发现关联。这项研究提供的证据表明，在NOS 2A启动子的单倍型影响结核病的易感性，并证实了NO的生产在疾病中的重要性。(C)2008爱思唯尔有限公司保留所有权利。
Chromosome 17 is known to contain TB susceptibility genes. Polymorphisms in two of these genes, namely NOS2A and CCL2, have been associated with TB in various populations. To investigate a possible association of gene variants with TB in the South African Coloured population we genotyped SNPs from NOS2A and CCL2 in over 800 TB cases and controls. We found a significant association between TB and two haplotypes, containing the functional rs9282799 and rs8078340 SNPs, in the NOS2A promoter. The T allele of rs8078340, found in the haplotype over-represented in cases (p = 0.015, pc = 0.038, OR = 1.4, 95% Cl [1.1 - 1.8]), was previously shown to decrease the quantity of DNA-protein complex bound as well as the duration of binding and may decrease nitric oxide (NO) production. The C allele of rs8078340 was present in the haplotype more frequent in controls (p = 0.011, pc = 0.029, OR = 1.4, 95% Cl [1.1 - 1.8]). In the single-point analysis of NOS2A, rs2779249 (previously associated with TB; in Brazilians) and the functional rs8078340 were nominally associated with disease. No association was found between any of the other SNPs or haplotypes studied and TB. This study presents evidence that haplotypes in the NOS2A promoter influence susceptibility to TB and confirms the importance of NO production in the disease. (C) 2008 Elsevier Ltd. All rights reserved.