Diabetes, Metabolic Syndrome and Obesity (Feb 2024)

IFN-γ, SCF, MIP1b and IL-16 Were Associated with Risk of Diabetic Nephropathy: A Mendelian Randomization Study

  • An L,
  • Ren X,
  • Pan Y,
  • Gao W,
  • Ren L,
  • Wang J,
  • Wang Y

Journal volume & issue
Vol. Volume 17
pp. 851 – 856

Abstract

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Li An,1,2,* Xiaomei Ren,1,* Ye Pan,2 Wei Gao,1 Liqun Ren,1 Jing Wang,3 Yao Wang2 1Department of Geriatrics, ZhongDa Hospital, Southeast University School of Medicine, Nanjing, 210009, People’s Republic of China; 2Department of Endocrine, ZhongDa Hospital, Southeast University School of Medicine, Nanjing, 210009, People’s Republic of China; 3Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, 211400, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Wang; Yao Wang, Tel/Fax +86-25- 83272111, Email [email protected]; [email protected]: The impact of inflammatory factors on the risk of diabetic nephropathy (DN) is inconsistent. Two-sample Mendelian randomization (MR) analyses were used to detect the causal role of inflammatory factors in DN risk.Methods: Inflammatory factor GWAS summary data were collected from a meta-analysis including 8,293 Finnish participants, and DN information was extracted from a GWAS of 213,746 individuals from FinnGen. The MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) outlier test was used for the removal of horizontal pleiotropic outliers. Multivariable MR analysis was also used to adjust for pleiotropy.Results: IFN-γ [ORIVW: 1.33; 95% CI: 1.09– 1.63; p=0.005] and SCF [ORIVW: 1.25, 1.02– 1.52; p = 0.027] were associated with an increased risk of DN. MIP1b [ORIVW: 0.92; 95% CI: 0.85– 0.98; p = 0.022] and IL-16 [ORIVW: 0.89, 0.81– 0.99; p = 0.043] showed negative associations with the risk of DN. We validated our MR results with MR-PRESSO analyses. Significant horizontal pleiotropy was not found. Moreover, in the multivariable MR analysis, the associations between cytokines and DN risk remained.Conclusion: Our MR results based on genetic data contribute to a better understanding of the pathogenesis of DN and provide evidence for a causal effect of inflammatory factors on DN. These findings support targeting specific inflammatory factors to alleviate DN risk.Keywords: causal association, diabetic nephropathy, inflammatory factors, Mendelian randomization

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