Wawrocki Sebastian, Kielnierowski Grzegorz, Rudnicka Wieslawa, Druszczynska Magdalena
Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz, Łódź, Poland.
Regional Specialized Hospital of Tuberculosis, Lung Diseases and Rehabilitation, Tuszyn, Poland.
Acta Biochim Pol. 2019 Jul 9;66(3):337-342. doi: 10.18388/abp.2019_2797.
Polymorphisms in genes encoding cytokines are known to determine susceptibility to Mycobacterium tuberculosis (M.tb) infection. In particular, interleukin-18 (IL-18), an inducer of interferon-gamma (IFN-γ), playing an important role in anti-mycobacterial immune responses, may influence the risk of developing active tuberculosis (TB).
A case-control study was performed to investigate whether two promoter polymorphisms of the IL-18 gene at positions -137G/A (rs187238) and -607A/C (rs1946518) affect the serum level of IL-18 and might be associated with genetic susceptibility to tuberculosis (TB) in the Polish population.
Two IL-18 gene promoter SNPs were detected by an allele-specific polymerase chain reaction. Serum IL-18 levels were measured immunoenzymatically using Human Total IL-18 ELISA DuoSet.
A single-gene analysis showed no differences either in allele or genotype frequencies of the studied SNPs between TB patients and healthy controls. No significant differences in the frequencies of any of the haplotypes between TB patients and healthy controls were found. None of the polymorphic variants of IL-18(-137G/A) or IL-18(-607A/C) SNP was associated with IL-18 producing capability.
Our results suggest that IL-18(-137G/A) and IL-18(-607A/C) polymorphisms may not be risk factors for susceptibility to TB in the Polish population. Increased serum IL-18 level observed in TB patients has no genetic background, but is a consequence of M.tb infection. Further studies with a higher sample size are required to confirm these findings.
已知编码细胞因子的基因多态性决定对结核分枝杆菌(M.tb)感染的易感性。特别是白细胞介素-18(IL-18),作为干扰素-γ(IFN-γ)的诱导剂,在抗分枝杆菌免疫反应中起重要作用,可能影响活动性结核病(TB)的发病风险。
进行一项病例对照研究,以调查IL-18基因位于-137G/A(rs187238)和-607A/C(rs1946518)位置的两个启动子多态性是否会影响IL-18的血清水平,以及是否可能与波兰人群中结核病(TB)的遗传易感性相关。
通过等位基因特异性聚合酶链反应检测两个IL-18基因启动子单核苷酸多态性。使用人总IL-18 ELISA DuoSet免疫酶法测量血清IL-18水平。
单基因分析显示,TB患者和健康对照之间,所研究的单核苷酸多态性的等位基因或基因型频率均无差异。TB患者和健康对照之间未发现任何单倍型频率的显著差异。IL-18(-137G/A)或IL-18(-607A/C)单核苷酸多态性的任何多态性变体均与IL-18产生能力无关。
我们的结果表明,IL-18(-137G/A)和IL-18(-607A/C)多态性可能不是波兰人群中结核病易感性的危险因素。TB患者中观察到的血清IL-18水平升高没有遗传背景,而是M.tb感染的结果。需要进一步进行更大样本量的研究来证实这些发现。