Guangdong Pharmaceutical University, Hai Zhu District, Guangzhou City, Guang Dong Province, China.
Trans R Soc Trop Med Hyg. 2021 Jan 7;115(1):20-29. doi: 10.1093/trstmh/traa076.
Tuberculosis (TB) is an important public health problem in China and environmental and genetic factors have an impact on its occurrence and development. We explored the relationship between environmental factors, genetic susceptibility genes and gene-environment interactions and the incidence of TB, as well as their high-risk combination, which can provide a scientific basis for prevention of the disease.
The 242 individuals, which included 82 TB patients, 67 family genetically related patients and 93 healthy controls, all of whom were of the Han population in Guangdong Province. The basic information of subjects was collected, including general conditions, behaviour habits, family environmental factors and blood samples. Two single nucleotides with potential functions (interleukin-10 [IL-10] rs1800896, interferon-γ [IFN-γ] rs2430561) were screened by bioinformatics tools and identified by polymerase chain reaction-restriction fragment length polymorphism.
We found that gender, education, TB exposure history, fitness activities, residential areas and indoor hygiene conditions were all associated with the occurrence of TB. In the dominant model, AG+GG of IL-10 and AA of IFN-γ are high-risk genotypes. Multifactor dimensionality reduction (MDR) analysis of TB-prone families shows that a combination of male sex, IL-10 AA and AG genotypes and smoking history are elements of high risk for TB infection (prediction accuracy 62.45%, cross-validation consistency 10/10). The MDR analysis of the TB patients group and the healthy control group showed that the combination of low education level, history of TB exposure, and IFN-γ AA genotype represented a higher risk of TB infection (prediction accuracy 80.34%, cross-validation consistency 10/10).
The occurrence of TB in TB-prone families in the Han population of Guangdong Province is related to environmental factors as well as cytokines IL-10 and IFN-γ. We also found high-risk combinations of genes and environmental factors, providing clues for the timely detection of high-risk groups.
结核病（TB）是中国重要的公共卫生问题，环境和遗传因素对其发生和发展有影响。我们探讨了环境因素、遗传易感基因和基因-环境相互作用与 TB 发病的关系及其高危组合，为该病的防治提供科学依据。
242 例个体，包括 82 例 TB 患者、67 例家族遗传相关患者和 93 例健康对照，均为广东省汉族人群。收集受试者的基本信息，包括一般情况、行为习惯、家庭环境因素和血样。通过生物信息学工具筛选出具有潜在功能的两个单核苷酸（白细胞介素-10[IL-10]rs1800896、干扰素-γ[IFN-γ]rs2430561），并通过聚合酶链反应-限制性片段长度多态性进行鉴定。
我们发现，性别、教育程度、TB 暴露史、健身活动、居住区域和室内卫生条件均与 TB 的发生有关。在显性模型中，IL-10 的 AG+GG 和 IFN-γ 的 AA 是高危基因型。TB 易感家族的多因子降维（MDR）分析显示，男性、IL-10AA 和 AG 基因型和吸烟史的组合是 TB 感染的高危因素（预测准确性 62.45%，交叉验证一致性 10/10）。TB 患者组和健康对照组的 MDR 分析显示，低教育水平、TB 暴露史和 IFN-γAA 基因型的组合代表了更高的 TB 感染风险（预测准确性 80.34%，交叉验证一致性 10/10）。
广东省汉族人群 TB 易感家族中 TB 的发生与环境因素以及细胞因子 IL-10 和 IFN-γ 有关。我们还发现了基因和环境因素的高危组合，为及时发现高危人群提供了线索。
