炎症因子与糖尿病肾病的因果关系:双向孟德尔随机化研究

Causal relationship between inflammatory factors and diabetic nephropathy:a bidirectional Mendelian randomization study

目的 采用孟德尔随机化方法探索炎症因子与糖尿病肾病之间潜在的因果关系。方法 使用炎症因子和糖尿病肾病的全基因组关联研究的摘要级数据,逆方差加权分析法用作主要分析方法,采用加权中位数、MR-Egger回归法、简单模型和中位模型方法进行结果补充。进行敏感性分析检验孟德尔随机化分析结果是否可靠。结果 在逆方差加权分析方法中,干细胞因子[OR=1.28,95%CI(1.04,1.58),P=0.020]和干扰素-γ[OR=1.36,95%CI(1.10,1.70),P=0.005]与糖尿病肾病风险呈正相关,糖尿病肾病与干扰素诱导蛋白10[OR=0.90,95%CI(0.83,0.98),P=0.012]之间存在负相关。敏感性分析结果显示孟德尔随机化分析结果可靠。结论 干细胞因子和干扰素-γ与发生糖尿病肾病风险增加有关,糖尿病肾病会减少体内干扰素诱导蛋白10的表达。炎症因子与糖尿病肾病发生之间存在潜在的因果关系。这一发现对糖尿病肾病的前期诊断及治疗具有一定的临床指导意义。

Objective This study applied Mendelian randomization to explore the potential causal relationship between inflammatory factors and diabetic nephropathy.Methods Summary-level data from genome-wide association studies of inflammatory factors and diabetic nephropathy were used,and inverse variance weighted analysis was used as the primary analytical method,complemented by results from weighted median,MR-Egger regression,simple model,and median model approaches.Sensitivity analysis was used to test the reliability of the MR analysis results.Results In the inverse variance weighted method,stem cell factor(OR=1.28,95%CI 1.04 to 1.58,P=0.020)and interferon-γ(OR=1.36,95%CI 1.10 to 1.70,P=0.005)were positively correlated with diabetic nephropathy,and diabetic nephropathy was positively correlated with interferon-inducible protein 10(OR=0.90,95%CI 0.83 to 0.98,P=0.012)were negatively correlated with diabetic nephropathy.Sensitivity analysis showed that MR analysis was reliable.Conclusion Stem cell factors and interferon-γare associated with an increased risk of developing diabetic nephropathy,and diabetic nephropathy decreases the expression of interferon-inducible protein 10 in vivo.Our results demonstrate a potential causal relationship between inflammatory factors and the development of diabetic nephropathy.This finding is of clinical significance for the pre-diagnosis and treatment of diabetic nephropathy.