Association of CTLA4 Gene Polymorphisms with Susceptibility and Pathology Correlation to Pulmonary Tuberculosis in Southern Han Chinese
Association of CTLA4 Gene Polymorphisms with Susceptibility and Pathology Correlation to Pulmonary Tuberculosis in Southern Han Chinese
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CTLA4基因多态性与南方汉族肺结核易感性及病理相关性的关系
DOI：
10.7150/ijbs.4390
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发表时间：
2012-01-01
影响因子：
9.2
通讯作者：
Li, Ji-Cheng
中科院分区：
文献类型：
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作者：
Wang, Chong;Jiang, Tingting;Li, Ji-Cheng
细胞毒性T淋巴细胞抗原-4（CTLA 4）基因是T淋巴细胞免疫应答的关键负调节因子。研究发现，CTLA 4 + 49 A>G（rs 231775）、+6230 G>A（rs3087243）和11430 G>A（rs 11571319）多态性与多种自身免疫性疾病的易感性相关，并可下调CTLA 4对细胞免疫应答的抑制作用。为揭示中国南方汉族人群肺结核的易感性和病理相关性，采用PCR和DNA测序方法对CTLA 4基因3个SNPs进行分型。结果发现，肺结核患者CTLA 4 + 49 AG基因型频率（38.42%）显著低于健康对照组（49.77%），（P-cor=0.038，OR = 0.653，95% CI = 0.436-0.978）。而另外2个SNP（+6230 G>A、11430 G>A）与结核病无相关性（P>0.05）。单倍型分析显示，健康对照组AGG单倍型频率（6.9%）显著高于肺结核组（1.4%）（P=0.005，P-cor=0.0002，OR0.183，95%CI0.072 -0.468）。单倍型GGA与双肺肺结核的相关性显著高于单肺结核（P-cor=0.042）。本研究首次报道CTLA 4基因的遗传变异与中国南方汉族人肺结核病的发病相关，CTLA 4 + 49 AG基因型和单倍型AGG可能降低中国南方汉族人感染肺结核病的风险。GGA单倍型与双肺结核相关，为阐明肺结核的发病机制提供了新的实验依据。
The cytotoxic T lymphocyte antigen-4 (CTLA4) gene is a key negative regulator of the T lymphocyte immune response. It has been found that CTLA4 + 49A>G (rs231775), + 6230G>A (rs3087243), and 11430G>A (rs11571319) polymorphisms are associated with susceptibility to many autoimmune diseases, and can down-regulate the inhibition of cellular immune response of CTLA4. Three SNPs in CTLA4 were genotyped by using the PCR and DNA sequencing methods in order to reveal the susceptibility and pathology correlation to pulmonary tuberculosis in Southern Han Chinese. We found that the frequency of CTLA4 + 49AG genotype in the pulmonary tuberculosis patients (38.42%) was significantly lower than that of the healthy controls (49.77%), (P-cor=0.038, OR 0.653, 95% CI 0.436-0.978). But, no associations were found between the other 2 SNPs (+ 6230G>A, 11430G>A) and tuberculosis (P>0.05). Haplotype analysis showed that the frequency of haplotype AGG in the healthy controls group (6.9%) was significantly higher than the pulmonary tuberculosis patients group (1.4%), (global P=0.005, P-cor=0.0002, OR 0.183, 95% CI 0.072-0.468). In addition, haplotype GGA was found to be significantly related to tuberculosis with double lung lesion rather than single lung lesion (P-cor=0.042). This study is the first to report that genetic variants in the CTLA4 gene can be associated with pulmonary tuberculosis in Southern Han Chinese, and CTLA4 + 49AG genotype as well as haplotype AGG may reduce the risk of being infected with pulmonary tuberculosis. The GGA haplotype was related to tuberculosis with double lung lesion, which provides a new experimental basis to clarify the pathogenesis of pulmonary tuberculosis.