Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, PR China.
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.
Gene. 2014 Jun 10;543(1):140-4. doi: 10.1016/j.gene.2014.03.042. Epub 2014 Mar 25.
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.
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).
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).
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.
遗传宿主因素在控制个体对病原体的易感性方面起着重要作用。本研究旨在探讨干扰素-γ（IFNG）及其受体（IFNGR1）的遗传多态性在中国人肺结核中的单倍型和联合作用。
本基于人群的病例对照研究包括 1434 例肺结核患者和 1412 例健康对照。采用 TaqMan 等位基因鉴别技术对 IFNG/IFNGR1 中的 6 个标签 SNP 进行基因分型。通过计算比值比（OR）和 95%置信区间（CI），采用 logistic 回归模型分析基因型和单倍型与结核病风险之间的关系。
经过多次比较的 Bonferroni 校正，IFNGR1 基因中的三个 SNP（rs2234711、rs1327475 和 rs7749390）与结核病风险的改变显著相关。对于 SNP rs2234711，与 T 等位基因（vs. C）相比，携带 C 等位基因的个体患结核病的风险降低，校正后的 OR（95%CI）为 0.82（0.76-0.91）。加性模型显示，每个额外的等位基因可降低约 14%的风险（OR：0.86，95%CI：0.77-0.95）。此外，我们观察到 rs2234711 与 rs3799488 之间存在很强的连锁不平衡。与常见的 rs2234711C-rs3799488C 单倍型相比，rs2234711T-rs3799488C 单倍型显著增加了结核病的风险（校正后的 OR：1.24，95%CI：1.09-1.41）。
我们的结果表明，IFNGR1 基因的遗传多态性与中国人群的结核病易感性有关。未来的研究应包括全面的测序分析，以确定观察到的关联背后的特定致病序列变异。
