Department of Urology, Huaiyin Hospital of Huai'an City, Huai'an, China.
Jiangyin Center for Disease Control and Prevention, Jiangyin, China.
BMC Urol. 2022 Aug 20;22(1):127. doi: 10.1186/s12894-022-01081-w.
Trefoil Factor 1 (TFF1) is considered to be able to inhibit the formation of kidney stone. However, genetic variants in TFF1 and corresponding function in kidney stone development are still not well studied. In this study, the discovery set including 230 cases and 250 controls was used to analyze the association between seven tagSNPs of TFF1 gene and the nephrolithiasis risk. Further evaluation was confirmed by the validation set comprising 307 cases and 461 controls. The consequences of the two-stage case-control study indicated that individuals with the rs3761376 A allele have significantly increased nephrolithiasis risk than those with the GG genotypes [adjusted odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.05-1.73]. Moreover, we also carried out a stratified analysis and found the increased nephrolithiasis risks at A allele among males, overweight individuals, no hypertensive individuals, nondiabetic individuals, smokers, and drinkers. In the following functional experiments, the notably lower expression of TFF1 was exhibited by the vectors carrying A allele compared with those carrying G allele in both luciferase (P = 0.022) and expression vectors (P = 0.041). In addition to tissue detection, we confirmed a significant inverse association of rs3761376 G > A and TFF1 gene expression (P < 0.001). These results suggest that TFF1 rs3761376 may serve as a potential biomarker to predict the risk of nephrolithiasis.
三叶因子 1（TFF1）被认为能够抑制肾结石的形成。然而，TFF1 中的遗传变异及其在肾结石形成中的相应功能仍未得到很好的研究。在这项研究中，使用包括 230 例病例和 250 例对照的发现集来分析 TFF1 基因的 7 个标签 SNP 与肾结石风险之间的关联。进一步的评估通过包括 307 例病例和 461 例对照的验证集得到确认。两阶段病例对照研究的结果表明，与 GG 基因型相比，携带 rs3761376A 等位基因的个体肾结石风险显著增加[校正优势比（OR）=1.35，95%置信区间（CI）=1.05-1.73]。此外，我们还进行了分层分析，发现 A 等位基因在男性、超重个体、非高血压个体、非糖尿病个体、吸烟者和饮酒者中增加了肾结石的风险。在随后的功能实验中，携带 A 等位基因的载体显示出明显低于携带 G 等位基因的载体的 TFF1 表达（P=0.022）和表达载体（P=0.041）。除了组织检测外，我们还证实 rs3761376G>A 与 TFF1 基因表达之间存在显著的负相关（P<0.001）。这些结果表明，TFF1 rs3761376 可能作为预测肾结石风险的潜在生物标志物。
