A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis.
A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis.
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DOI：
10.1084/jem.20050126
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发表时间：
2005-12-19
期刊：
影响因子：
--
通讯作者：
Granados J
中科院分区：
文献类型：
--
作者：
Flores-Villanueva PO;Ruiz-Morales JA;Song CH;Flores LM;Jo EK;Montaño M;Barnes PF;Selman M;Granados J
我们检测了墨西哥结核病患者和健康对照组中一氧化氮合酶2A、单核细胞趋化蛋白-1（MCP-1）、活化调节、正常T细胞表达和分泌以及巨噬细胞炎性蛋白-1 α基因的单核苷酸多态性（SNP）分布。MCP-1基因型AG和GG携带者发生结核病的几率是纯合子AA携带者的2.3倍和5.4倍。GG纯合子患者血浆MCP-1水平最高，IL-12p40水平最低，且这些值呈负相关。此外，刺激的单核细胞基因型GG与结核分枝杆菌抗原的健康载体产生更高的MCP-1和更低的IL-12p40浓度比平行实验与单核细胞纯合子AA。抗MCP-1抗体的加入增加了M.结核病刺激的来自纯合子GG的单核细胞，并且添加外源性MCP-1减少M.来自纯合AA的结核病刺激的单核细胞。此外，我们可以在韩国受试者中复制我们的结果，MCP-1基因型AG和GG携带者患结核病的几率比纯合子AA高2.8倍和6.9倍。我们的研究结果表明，携带MCP-1基因型GG的人产生高浓度的MCP-1，其抑制响应于M.结核病并增加M.肺结核感染会发展为活动性肺结核。
We examined the distribution of single nucleotide polymorphisms (SNPs) in nitric oxide synthase 2A, monocyte chemoattractant protein–1 (MCP-1), regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein–1 α genes in tuberculosis patients and healthy controls from Mexico. The odds of developing tuberculosis were 2.3- and 5.4-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Cases of homozygous GG had the highest plasma levels of MCP-1 and the lowest plasma levels of IL-12p40, and these values were negatively correlated. Furthermore, stimulation of monocytes from healthy carriers of the genotype GG with Mycobacterium tuberculosis antigens yielded higher MCP-1 and lower IL-12p40 concentrations than parallel experiments with monocytes from homozygous AA. Addition of anti–MCP-1 increased IL-12p40 levels in cultures of M. tuberculosis–stimulated monocytes from homozygous GG, and addition of exogenous MCP-1 reduced IL-12p40 production by M. tuberculosis–stimulated monocytes from homozygous AA. Furthermore, we could replicate our results in Korean subjects, in whom the odds of developing tuberculosis were 2.8- and 6.9-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Our findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which inhibits production of IL-12p40 in response to M. tuberculosis and increases the likelihood that M. tuberculosis infection will progress to active pulmonary tuberculosis.
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DOI：
10.1084/jem.175.4.1111
发表时间：
1992-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan J;Xing Y;Magliozzo RS;Bloom BR
通讯作者：
Bloom BR
DOI：
10.1084/jem.169.1.59
发表时间：
1989-01-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Heinzel FP;Sadick MD;Holaday BJ;Coffman RL;Locksley RM
通讯作者：
Locksley RM
影响因子：
4.4
作者：
Braun, MC;Lahey, E;Kelsall, BL
通讯作者：
Kelsall, BL
DOI：
10.1098/rstb.1997.0118
发表时间：
1997-09-29
影响因子：
6.3
作者：
Blackwell, JM;Black, GF;Shaw, MA
通讯作者：
Shaw, MA
影响因子：
158.5
作者：
Bellamy, R;Ruwende, C;Hill, AVS
通讯作者：
Hill, AVS