中国人群中 TYK2 内遗传变异与肺结核的关联。
Associations of genetic variants within TYK2 with pulmonary tuberculosis among Chinese population.
机构信息
Tuberculosis Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou City, China.
出版信息
Mol Genet Genomic Med. 2024 Feb;12(2):e2386. doi: 10.1002/mgg3.2386.
BACKGROUND
Pulmonary tuberculosis (PTB) is a common infectious disease caused by mycobacterium tuberculosis (MTB) and the present study aims to explore the associations of genetic variants within tyrosine kinases 2 (TYK2) with PTB incidence.
METHODS
A population-based case control study including 168 smear-positive PTB cases and 251 controls was conducted. Five single nucleotide polymorphisms (SNPs) including rs280520, rs91755, rs2304256, rs12720270, rs280519 located within TYK2 gene were selected and MassARRAY® MALDI-TOF system was employed for genotyping. SPSS 19.0 was adopted for statistical analysis, non-conditional logistic regression was conducted. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were computed to estimate their contributions to PTB incidence.
RESULTS
In the overall study population, rs91755 TT and rs280519 AA genotypes were found to be associated with reduced PTB risk (OR = 0.34, 95% CI: 0.16-0.72; OR = 0.38, 95% CI: 0.18-0.79, respectively). After stratification for sex, we found that among the male population, rs91755TG/TT, rs12720270AG/GG and rs280519AG/AA genotypes were associated with reduced PTB risk (OR = 0.41, 95% CI: 0.21-0.80; OR = 0.44, 95% CI: 0.21-0.94; OR = 0.42, 95% CI: 0.21-0.82, respectively). After stratification for age, we found that among those aged <60 years, rs91755TT and rs280519AA genotype were associated with reduced PTB risk (OR = 0.29, 95% CI: 0.09-0.90; OR = 0.34, 95% CI: 0.11-1.08, respectively); while rs2304256AC/AA genotype was associated with increased PTB risk (OR = 2.68, 95% CI: 1.05-6.85). Haplotype analysis revealed that AGAAG and ATCGA (Combined with rs280520, rs91755, rs2304256, rs12720270 and rs280519) were associated with increased (OR = 1.54, 95% CI: 1.01-2.37) and decreased PTB risk (OR = 0.70, 95% CI: 0.52-0.94), respectively.
CONCLUSIONS
The genetic variants located within TYK2 including rs91755, rs12720270 and rs280519 were found to be associated with modified PTB risk and the SNPs had potential to be the biomarkers to predict PTB incidence risk.
背景
肺结核（PTB）是一种由结核分枝杆菌（MTB）引起的常见传染病，本研究旨在探讨酪氨酸激酶 2（TYK2）内的遗传变异与 PTB 发生率之间的关系。
方法
本研究采用基于人群的病例对照研究，包括 168 例痰涂片阳性 PTB 病例和 251 例对照。选择了位于 TYK2 基因内的五个单核苷酸多态性（SNP），包括 rs280520、rs91755、rs2304256、rs12720270 和 rs280519，采用 MassARRAY® MALDI-TOF 系统进行基因分型。采用 SPSS 19.0 进行统计分析，采用非条件逻辑回归。计算比值比（OR）和 95%置信区间（95%CI）来估计它们对 PTB 发生率的贡献。
结果
在整个研究人群中，发现 rs91755 TT 和 rs280519 AA 基因型与降低 PTB 风险相关（OR=0.34，95%CI：0.16-0.72；OR=0.38，95%CI：0.18-0.79）。按性别分层后，我们发现男性人群中 rs91755TG/TT、rs12720270AG/GG 和 rs280519AG/AA 基因型与降低 PTB 风险相关（OR=0.41，95%CI：0.21-0.80；OR=0.44，95%CI：0.21-0.94；OR=0.42，95%CI：0.21-0.82）。按年龄分层后，我们发现年龄<60 岁的人群中 rs91755TT 和 rs280519AA 基因型与降低 PTB 风险相关（OR=0.29，95%CI：0.09-0.90；OR=0.34，95%CI：0.11-1.08）；而 rs2304256AC/AA 基因型与增加 PTB 风险相关（OR=2.68，95%CI：1.05-6.85）。单倍型分析显示，AGAAG 和 ATCGA（与 rs280520、rs91755、rs2304256、rs12720270 和 rs280519 联合）与增加（OR=1.54，95%CI：1.01-2.37）和降低 PTB 风险（OR=0.70，95%CI：0.52-0.94）相关。
结论
位于 TYK2 内的遗传变异，包括 rs91755、rs12720270 和 rs280519，与改良的 PTB 风险相关，这些 SNP 有可能成为预测 PTB 发病率风险的生物标志物。
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