Synergy factor analysis.

Urolithiasis is one of the most common urological diseases worldwide with an unclear aetiology. However, a growing body of evidence suggests the potential role of molecular disturbances of the inflammation as well as oxidative and nitrative stresses, in the pathogenesis of urolithiasis. Therefore, we aimed to detect the potential association between six selected single-nucleotide polymorphisms (SNPs) and the development of nephrolithiasis. Moreover, we verified the association of urolithiasis development and mRNA expression of IL-6, IL-8, SOD2, and NOS2 in peripheral blood mononuclear cells (PBMCs). Total genomic DNA and mRNA were isolated from the peripheral blood of 112 patients with urolithiasis and 114 healthy subjects. Using Taq-Man® probes, we genotyped the following SNPs: rs1800797 and rs2069845 in IL-6, rs2227307 in IL-8, rs4880 in SOD2, rs2297518 and rs2779249 in NOS2. In turn, the evaluation of mRNA expression was performed using real-time PCR and 2-ΔCt methods. We found that the C/T genotype of the c.47 T>C–SOD2 SNP increased the frequency of urolithiasis occurrence whereas the T/T homozygote of the same polymorphism decreased the risk of urolithiasis development in the Polish population. Moreover, our study confirmed that patients with urolithiasis were characterised by decreased IL-6, IL-8, and SOD2 mRNA expression levels compared to the controls. In conclusion, our results suggest that polymorphic variants and changes in mRNA expression of IL-6, IL8, SOD2, and NOS2 may be involved in the pathophysiology of urolithiasis.

尿石症（Urolithiasis）是全球最常见的泌尿外科疾病之一，其病因学尚未明确。不过，越来越多的研究证据表明，炎症分子紊乱、氧化应激与硝化应激可能在尿石症的发病机制中发挥潜在作用。因此，本研究旨在探究6个选定的单核苷酸多态性（single-nucleotide polymorphisms, SNPs）与肾结石症（nephrolithiasis）发生之间的潜在关联。此外，本研究还验证了尿石症的发生与外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）中IL-6、IL-8、SOD2及NOS2的mRNA表达水平的相关性。研究人员从112例尿石症患者及114例健康受试者的外周血中提取了总基因组DNA与mRNA。利用Taq-Man®探针，对以下SNPs进行基因分型：IL-6基因中的rs1800797与rs2069845、IL-8基因中的rs2227307、SOD2基因中的rs4880，以及NOS2基因中的rs2297518与rs2779249。另一方面，采用实时荧光定量PCR（real-time PCR）与2-ΔCt法完成mRNA表达水平的检测。研究结果显示，在波兰人群中，c.47 T>C–SOD2 SNP的C/T基因型会升高尿石症的发生频率，而该多态性位点的T/T纯合子则会降低尿石症的发病风险。此外，本研究证实，与健康对照组相比，尿石症患者的IL-6、IL-8及SOD2的mRNA表达水平显著降低。综上，本研究结果提示，IL-6、IL-8、SOD2及NOS2的多态性变异与mRNA表达变化可能参与尿石症的病理生理过程。