Tag SNP polymorphism of CCL2 and its role in clinical tuberculosis in Han Chinese pediatric population.

Tag SNP polymorphism of CCL2 and its role in clinical tuberculosis in Han Chinese pediatric population.
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DOI:
10.1371/journal.pone.0014652
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发表时间:
2011-02-04
期刊:
影响因子:
3.7
通讯作者:
Shen A
Shen A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Feng WX;Mokrousov I;Wang BB;Nelson H;Jiao WW;Wang J;Sun L;Zhou SR;Xiao J;Gu Y;Wu XR;Ma X;Shen A

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趋化因子(C-C基序)配体2 CCL 2/MCP-1是先天免疫的关键信号分子之一;特别是,它参与单核细胞和其他细胞响应感染(包括结核病(TB))的募集,并且是肉芽肿形成所必需的。我们鉴定了CCL 2/MCP-1基因的标签SNP(rs 4586 C/T)。为了了解该SNP是否可用于评估CCL 2基因对TB疾病表达的贡献,我们进一步分析了其等位基因和基因型在301例TB病例和338例非感染对照(均接种BCG)中的分布,这些病例代表了中国北方的高危儿科人群。在男性TB亚组中,C等位基因的检出率更高(P = 0.045),并且是临床TB的主要危险因素(P = 0.029)。    纯合子TT基因型与结核性脑膜炎(TBM)患者CSF单核细胞(ML)计数降低显著相关(P = 0.001)。  本研究发现CCL 2标签SNP rs 4586 C等位基因与男性儿童结核病相关,表明性别可能影响儿童对结核病的易感性。纯合TT基因型与CSF单核白细胞(ML)计数降低的相关性不仅表明该SNP的临床意义,而且表明其有助于疑似TBM的临床评估的潜力,其中延迟是至关重要的,诊断是困难的。
Chemokine (C-C motif) ligand 2 CCL2/MCP-1 is among the key signaling molecules of innate immunity; in particular, it is involved in recruitment of mononuclear and other cells in response to infection, including tuberculosis (TB) and is essential for granuloma formation. We identified a tag SNP for the CCL2/MCP-1 gene (rs4586 C/T). In order to understand whether this SNP may serve to evaluate the contribution of the CCL2 gene to the expression of TB disease, we further analysed distribution of its alleles and genotypes in 301 TB cases versus 338 non-infected controls (all BCG vaccinated) representing a high-risk pediatric population of North China. In the male TB subgroup, the C allele was identified in a higher rate (P = 0.045), and, acting dominantly, was found to be a risk factor for clinical TB (P = 0.029). Homozygous TT genotype was significantly associated with lower CSF mononuclear leukocyte (ML) counts in patients with tuberculous meningitis (TBM) (P = 0.001). The present study found an association of the CCL2 tag SNP rs4586 C allele and pediatric TB disease in males, suggesting that gender may affect the susceptibility to TB even in children. The association of homozygous TT genotype with decreased CSF mononuclear leukocyte (ML) count not only suggests a clinical significance of this SNP, but indicates its potential to assist in the clinical assessment of suspected TBM, where delay is critical and diagnosis is difficult.
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