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Association of CTLA4 gene polymorphisms with susceptibility and pathology correlation to pulmonary tuberculosis in Southern Han Chinese.

ABSTRACT: 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.

SUBMITTER: Wang C

PROVIDER: S-EPMC3399317 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Association of CTLA4 gene polymorphisms with susceptibility and pathology correlation to pulmonary tuberculosis in Southern Han Chinese.

Wang Chong C Jiang Tingting T Wei Liliang L Li Fujian F Sun Xiaojun X Fan Dapeng D Liu Jiyan J Zhang Xing X Xu Dandan D Chen Zhongliang Z Li Zhongjie Z Fu Xiaoyan X Li Ji-Cheng JC

International journal of biological sciences 20120710 7

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 corre ...[more]

PMID: 22811616

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Project description:BackgroundTuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, is a major public health concern. Chemokines and their receptors, such as RANTES, CXCR3, and CCR5, have been reported to play important roles in cell activation and migration in immune responses against TB infection.MethodsTo understand the correlations involving CCR5 gene variations, M. tuberculosis infection, and TB disease progression, a case-control study comprising 450 patients with TB and 306 healthy controls from a Chinese Han population was conducted, along with the detection of polymorphisms in the CCR5 promoter using a sequencing method.ResultsAfter adjustment for age and gender, the results of logistic analysis indicated that the frequency of rs2734648-G was significantly higher in the TB patient group (P = 0.002, OR = 1.38, 95% CI: 1.123-1.696); meanwhile, rs2734648-GG showed notable susceptibility to TB (P = 6.32E-06, OR = 2.173, 95% CI: 1.546-3.056 in a recessive model). The genotypic frequency of rs1799987 also varied between the TB and control groups (P = 0.008). In stratified analysis, rs2734648-GG significantly increased susceptibility to pulmonary TB in a recessive model (P < 0.0001, OR = 2.382, 95% CI: 1.663-3.413), and the rs2734648-G allele significantly increased susceptibility to TB recurrence in a dominant model (P = 0.0032, OR = 1.936, 95% CI: 1.221-3.068), whereas rs1799987-AA was associated with susceptibility to pulmonary TB (P = 0.0078, OR = 1.678, 95% CI: 1.141-2.495 in a recessive model) but not with extra-pulmonary TB and TB recurrence. A haplotype constructed with the major alleles of the eight SNPs in the CCR5 promoter (rs2227010-rs2856758-rs2734648-rs1799987-rs1799988-rs41469351-rs1800023-rs1800024: A-A-G-G-T-C-G-C) exhibited extraordinarily increased risk of susceptibility to TB and pulmonary TB (P = 6.33E-11, OR = 24.887, 95% CI: 6.081-101.841).ConclusionIn conclusion, CCR5 promoter polymorphisms were found to be associated with pulmonary TB and TB progression in Chinese Han people.

Dataset Information

Association of CTLA4 gene polymorphisms with susceptibility and pathology correlation to pulmonary tuberculosis in Southern Han Chinese.

Publications

Association of CTLA4 gene polymorphisms with susceptibility and pathology correlation to pulmonary tuberculosis in Southern Han Chinese.

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