Varzari Alexander, Tudor Elena, Bodrug Nina, Corloteanu Andrei, Axentii Ecaterina, Deyneko Igor V
1 Laboratory of Human Genetics, Chiril Draganiuc Institute of Phthisiopneumology , Kishinev, Republic of Moldova .
2 Hannover Unified Biobank, Hannover Medical School , Hannover, Germany .
Genet Test Mol Biomarkers. 2018 May;22(5):281-287. doi: 10.1089/gtmb.2017.0250. Epub 2018 Apr 2.
Chemokines play a key role in immune regulation and response, and have been implicated in the pathogenesis of tuberculosis (TB). In this study, we investigated whether functional polymorphisms of the chemokines CCL5, CCL2, and CXCL8 are associated with pulmonary TB in a Moldavian population.
A total of 250 patients with TB and 184 healthy controls were screened for CCL5 -403G/A (rs2107538), CCL5 In1.1T/C (rs2280789), CCL2 -2518A/G (rs1024611), and CXCL8 -251A/T (rs4073) polymorphisms using standard polymerase chain reaction techniques.
None of the analyzed variants were found to be significantly associated with overall pulmonary TB susceptibility. However, the CCL5 In1.1T/C polymorphism was significantly associated with early-onset TB in patients younger than 30 (dominant model, odds ratio [OR] = 3.01, p = 0.0046) or younger than 40 years (dominant model, OR = 2.17, p = 0.0099), and the conducted case-only analysis demonstrated that CCL5 In1.1T/C C-allele carriers exhibited an earlier TB onset than TT homozygotes (36.14 years vs. 40.13 years, p = 0.0065). In addition, nominal significance was observed for an association between TB incidence and both the eight paired genotypes in the overall patient cohort (0.017 < p < 0.05) and the CCL2 -2518A/G polymorphism among males (dominant model, OR = 0.55, p = 0.041; log-additive model, OR = 0.57, p = 0.018).
The CCL5 In1.1T/C polymorphism may modulate pulmonary early-onset TB risk.
趋化因子在免疫调节和反应中起关键作用，并与结核病（TB）的发病机制有关。在本研究中，我们调查了趋化因子CCL5、CCL2和CXCL8的功能多态性是否与摩尔多瓦人群中的肺结核相关。
使用标准聚合酶链反应技术，对250例结核病患者和184例健康对照进行CCL5 -403G/A（rs2107538）、CCL5 In1.1T/C（rs2280789）、CCL2 -2518A/G（rs1024611）和CXCL8 -251A/T（rs4073）多态性的筛查。
未发现所分析的变异与总体肺结核易感性显著相关。然而，CCL5 In1.1T/C多态性与30岁以下患者（显性模型，优势比[OR]=3.01，p=0.0046）或40岁以下患者（显性模型，OR=2.17，p=0.0099）的早发型肺结核显著相关，且仅病例分析表明，CCL5 In1.1T/C C等位基因携带者的肺结核发病时间早于TT纯合子（36.14岁对40.13岁，p=0.0065）。此外，在总体患者队列中，观察到肺结核发病率与8种配对基因型之间存在名义显著性（0.017 < p < 0.05），在男性中CCL2 -2518A/G多态性也存在名义显著性（显性模型，OR=0.55，p=0.041；对数加性模型，OR=0.57，p=0.018）。
CCL5 In1.1T/C多态性可能调节肺结核早发型风险。
