The causal association between cardiovascular proteins and diabetic nephropathy: a Mendelian randomization study.

Abstract

Purpose: To clarify the causal association between cardiovascular proteins and diabetic nephropathy (DN) in Europeans.

Methods: The large genome-wide association study data of cardiovascular proteins and DN were used for this two-sample Mendelian randomization (MR) analysis. We took the Inverse variance weighted (IVW) as the primary method. Moreover, MR-Egger, weighted median, weighted mode, and simple mode were also performed as supplementary methods. Further, Cochrane's Q test, MR-Egger, and MR-PRESSO were conducted for sensitivity analysis.

Results: According to the IVW method, the results indicated that Galanin peptide was a protective factor for DN (OR: 0.835, 95% CI 0.700, 0.996, P = 0.045) and seven cardiovascular proteins were identified as the risk factors for DN, including CX3CL1 (OR: 1.288, 95% CI 1.012, 1.639, P = 0.039), stem cell factor (OR: 1.228, 95%CI: 1.013, 1.489, P = 0.036), tumor necrosis factor receptor 2 (OR: 1.633, 95% CI 1.141, 2.338, P = 0.007), myeloperoxidase (OR: 1.412, 95% CI 1.103, 1.808, P = 0.006), galectin-3 (OR: 1.297, 95% CI 1.095, 1.537, P = 0.003), platelet-derived growth factor subunit B (OR: 1.338, 95% CI 1.020, 1.756, P = 0.035), and interleukin-27 (OR: 1.248, 95% CI 1.033, 1.509, P = 0.022). Moreover, the reverse MR study did not observe the causal effect of DN on cardiovascular proteins. The results of sensitivity analysis suggested no significant pleiotropy and heterogeneity.

Conclusion: This MR analysis first evaluated the causal relationship between cardiovascular protein and DN at the genetic level, which could be of great significance for the prevention and treatment of DN.