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. 2024 Dec 31;13(12):2724-2734.
doi: 10.21037/tau-24-378. Epub 2024 Dec 28.

A Mendelian randomization study on associations between plasma lipidome, circulating inflammatory proteins, and erectile dysfunction

Jiacheng Yu  1 , Peihe Liang  1
Affiliations

A Mendelian randomization study on associations between plasma lipidome, circulating inflammatory proteins, and erectile dysfunction

Jiacheng Yu et al. Transl Androl Urol. .

Abstract

Background: Some studies suggest a potential association between plasma lipidome and erectile dysfunction (ED), but the underlying mechanism and whether circulating inflammatory proteins act as mediators remain unclear. The purpose of this study was to investigate the potential causal relationships between plasma lipidome, inflammatory proteins, and ED.

Methods: Plasma lipidome, circulating inflammatory proteins, and ED cases were identified based on the summary data from several large-scale genome-wide association studies (GWAS). The causal relationships of plasma lipidome and circulating inflammatory proteins with ED were explored by a bidirectional two-sample, two-sample Mendelian randomization (MR) method. The inverse variance weighted (IVW) method was used as the primary analytical method. MR-Egger and the weighted median (IVW) methods were utilized as supplementary analytical techniques. Sensitivity analyses including MR-Pleiotropy RESidual Sum and Outlier method (PRESSO), Cochran's Q test, and MR-Egger intercept test were conducted to address heterogeneity and horizontal pleiotropy.

Results: Ceramide (d42:2) and triacylglycerol (56:3) were found to be associated with an increased risk of ED, while phosphatidylethanolamine (O-18:1_18:2) and phosphatidylinositol (18:1_18:1) were linked to a decreased risk of ED. Interleukin-1α (IL-1α), IL-7, IL-17C, and the tumor necrosis factor (TNF) receptor superfamily member 9 (TNFRSF9) positively affected ED. Conversely, leukemia inhibitory factor and urokinase-type plasminogen activator (uPA) showed a negative impact. Mediation analysis indicated that the uPA mediated between Triacylglycerol (56:3) and ED, accounting for a mediation proportion of -14.71%.

Conclusions: There was a causal relationship between plasma lipidome and circulating inflammatory proteins with ED. Circulating inflammatory proteins appeared to mediate between triacylglycerol (56:3) levels and ED.

Keywords: Mendelian randomization (MR); circulating inflammatory proteins; erectile dysfunction (ED); plasma lipidome.

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Conflict of interest statement

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-378/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The workflow of this study. ①, ②, ③, correspond to the three core assumptions of MR analysis. ED, erectile dysfunction; SNP, single nucleotide polymorphism; MR, Mendelian randomization; IVW, inverse variance-weighted; PRESSO, Pleiotropy RESidual Sum and Outlier method.
Figure 2
Figure 2
Volcano map of Mendelian randomization analysis between plasma lipidome, inflammatory proteins and erectile dysfunction. (A) Mendelian randomization analysis between plasma lipidome and ED; (B) Mendelian randomization analysis between inflammatory proteins and ED. ED, erectile dysfunction.
Figure 3
Figure 3
Mendelian randomization results of causal effects between plasma lipidome, circulating inflammatory proteins and erectile dysfunction. nSNP, number of single nucleotide polymorphism; OR, odds ratio; CI, confidence interval; MR, Mendelian randomization; PRESSO, Pleiotropy RESidual Sum and Outlier method.
Figure 4
Figure 4
The mediation effect of urokinase-type plasminogen activator in the causal effect of triacylglycerol (56:3) on ED risk. ED, erectile dysfunction.
See this image and copyright information in PMC

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