Jieqiong Lü1, Hongqiu Pan2, Yongzhong Chen3, Shaowen Tang1, Yan Feng1, Sangsang Qiu1, Siming Zhang1, Liang Wu1, Ruobing Xu1, Xianzhen Peng1, Jianming Wang4, Cheng Lu5. 1. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, PR China. 2. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, PR China; Department of Tuberculosis, Third Hospital of Zhenjiang City, Zhenjiang 212005, PR China. 3. Department of Tuberculosis, Third Hospital of Zhenjiang City, Zhenjiang 212005, PR China. 4. Department of Tuberculosis, Third Hospital of Zhenjiang City, Zhenjiang 212005, PR China. Electronic address: jmwang@njmu.edu.cn. 5. Department of Breast, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing 210004, PR China. Electronic address: lucheng66@126.com.
Abstract
OBJECTIVE: Genetic host factors play an important role in controlling individual's susceptibility to the pathogen. This study aims to explore the single and joint effect of genetic polymorphisms of interferon-gamma (IFNG) and its receptor (IFNGR1) in association with the pulmonary tuberculosis in a Chinese Han population. METHODS: This population-based case control study consisted of 1434 pulmonary tuberculosis patients and 1412 healthy controls. Six tag SNPs in IFNG/IFNGR1 were genotyped using TaqMan allelic discrimination technology. The logistic regression model was carried out to analyze the associations between the genotypes and haplotypes and the risk of tuberculosis by calculating the odds ratio (OR) and 95% confidence interval (CI). RESULTS: After the Bonferroni correction for multiple comparisons, three SNPs (rs2234711, rs1327475 and rs7749390) in IFNGR1 gene were observed to be significantly associated with the altered risks of tuberculosis. For the SNP rs2234711, individuals carrying C allele (vs. T) showed a decreased risk, with the adjusted OR(95% CI) of 0.82(0.76-0.91). The additive model revealed that each additional allele contributed about 14% decreased risk (OR: 0.86, 95% CI: 0.77-0.95). Moreover, we observed a strong linkage disequilibrium between rs2234711 and rs3799488. Compared with the common rs2234711C-rs3799488C haplotype, the haplotype rs2234711T-rs3799488C contributed to a significant increase in the risk of tuberculosis (adjusted OR: 1.24, 95% CI: 1.09-1.41). CONCLUSIONS: Our results suggest that genetic polymorphisms in IFNGR1 gene are involved in the risk of tuberculosis in the Chinese population. Future studies should include a comprehensive sequencing analysis to identify the specific causative sequence variants underlying the observed associations.
OBJECTIVE: Genetic host factors play an important role in controlling individual's susceptibility to the pathogen. This study aims to explore the single and joint effect of genetic polymorphisms of interferon-gamma (IFNG) and its receptor (IFNGR1) in association with the pulmonary tuberculosis in a Chinese Han population. METHODS: This population-based case control study consisted of 1434 pulmonary tuberculosispatients and 1412 healthy controls. Six tag SNPs in IFNG/IFNGR1 were genotyped using TaqMan allelic discrimination technology. The logistic regression model was carried out to analyze the associations between the genotypes and haplotypes and the risk of tuberculosis by calculating the odds ratio (OR) and 95% confidence interval (CI). RESULTS: After the Bonferroni correction for multiple comparisons, three SNPs (rs2234711, rs1327475 and rs7749390) in IFNGR1 gene were observed to be significantly associated with the altered risks of tuberculosis. For the SNP rs2234711, individuals carrying C allele (vs. T) showed a decreased risk, with the adjusted OR(95% CI) of 0.82(0.76-0.91). The additive model revealed that each additional allele contributed about 14% decreased risk (OR: 0.86, 95% CI: 0.77-0.95). Moreover, we observed a strong linkage disequilibrium between rs2234711 and rs3799488. Compared with the common rs2234711C-rs3799488C haplotype, the haplotype rs2234711T-rs3799488C contributed to a significant increase in the risk of tuberculosis (adjusted OR: 1.24, 95% CI: 1.09-1.41). CONCLUSIONS: Our results suggest that genetic polymorphisms in IFNGR1 gene are involved in the risk of tuberculosis in the Chinese population. Future studies should include a comprehensive sequencing analysis to identify the specific causative sequence variants underlying the observed associations.
Authors: Catherine M Stein; Lindsay Sausville; Christian Wejse; Rafal S Sobota; Nicola M Zetola; Philip C Hill; W Henry Boom; William K Scott; Giorgio Sirugo; Scott M Williams Journal: Curr Genet Med Rep Date: 2017-10-12
Authors: Dhêmerson Souza de Lima; Mauricio Morishi Ogusku; Maisa Porto Dos Santos; Cláudia Maria de Melo Silva; Vanessa Alves de Almeida; Irineide Assumpção Antunes; Antonio Luiz Boechat; Rajendranath Ramasawmy; Aya Sadahiro Journal: PLoS One Date: 2016-02-22 Impact factor: 3.240