Department of Immunology, Tuberculosis Research Centre, Indian Council of Medical Research, Chennai, India.
Int J Immunogenet. 2011 Oct;38(5):397-402. doi: 10.1111/j.1744-313X.2011.01021.x. Epub 2011 Jun 27.
The chemokine CCL5 is known to play an important role in the formation of granuloma during infection with Mycobacterium tuberculosis. Production of CCL5 is influenced by polymorphisms in the CCL5 gene. Hence, in the present study, we investigated whether polymorphisms in the promoter and intron regions of CCL5 gene are associated with susceptibility or resistance to pulmonary tuberculosis in south Indian population. Polymorphisms in the promoter (-403G/A and -28C/G) and intron (In1.1T/C) regions of CCL5 gene were studied in 212 pulmonary tuberculosis (PTB) patients and 213 healthy controls (HCs). Allele and genotype frequencies of CCL5 gene polymorphisms were not different between PTB patients and HCs. When the haplotype and diplotype frequencies were compared, a significantly decreased frequencies of the haplotype A-C-C [P = 0.037; Odds ratio (OR): 0.57; 95% confidence interval (CI): 0.34-0.97] and the diplotype G/A-T/C (P = 0.017; OR: 0.46; 95% CI: 0.24-0.88) were observed among PTB patients when compared with HCs. However, the significant differences observed for the haplotype and the diplotype were lost when corrected for multiple comparisons [Bonferroni correction: A-C-C P corrected (P(c) ) = 0.148 and G/A-T/C P(c) = 0.136]. Though the present results suggest that the CCL5 gene haplotype A-C-C and the diplotype G/A-T/C may be associated with resistance to PTB, further studies with increased sample size may be useful to confirm this present finding as well as to understand the role of CCL5 haplotype and diplotype on genetic susceptibility to TB.
趋化因子 CCL5 已知在感染结核分枝杆菌时在肉芽肿的形成中发挥重要作用。CCL5 的产生受 CCL5 基因多态性的影响。因此，在本研究中，我们研究了 CCL5 基因启动子和内含子区域的多态性是否与印度南部人群的肺结核易感性或抗性相关。研究了 212 例肺结核 (PTB) 患者和 213 例健康对照者 (HC) 中 CCL5 基因启动子 (-403G/A 和 -28C/G) 和内含子 (In1.1T/C) 区域的多态性。PTB 患者和 HCs 之间 CCL5 基因多态性的等位基因和基因型频率无差异。当比较单体型和双单体型频率时，发现 A-C-C 单体型 [P=0.037；优势比 (OR)：0.57；95%置信区间 (CI)：0.34-0.97] 和 G/A-T/C 双单体型 (P=0.017；OR：0.46；95% CI：0.24-0.88) 的频率显著降低在 PTB 患者中与 HCs 相比。然而，当进行多次比较校正时，单体型和双单体型的显著差异消失 [Bonferroni 校正：A-C-C P 校正 (P(c))=0.148 和 G/A-T/C P(c)=0.136]。尽管目前的结果表明 CCL5 基因单体型 A-C-C 和双单体型 G/A-T/C 可能与 PTB 的抗性相关，但进一步增加样本量的研究可能有助于证实这一发现，并了解 CCL5 单体型和双单体型对结核病遗传易感性的作用。
