Causal relationship between immune cells, inflammatory cytokines, metabolites, and erectile dysfunction: a two-sample Mendelian randomization study.

Autor:	Pang H; Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China., Liang Z; Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China., Hu C; Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China., Shao Y; Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China., Kong L; Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China., Cheng M; Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China., Du H; Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China., Yao L; National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, China., Liu F; Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China.
Jazyk:	angličtina
Zdroj:	Translational andrology and urology [Transl Androl Urol] 2024 Nov 30; Vol. 13 (11), pp. 2448-2458. Date of Electronic Publication: 2024 Nov 27.
DOI:	10.21037/tau-24-395
Abstrakt:	Background: Previous studies have investigated the association between immune inflammation, metabolism and erectile dysfunction (ED). However, these studies are limited by biases, confounding factors, and reverse causality, failing to establish causality. We conducted a two-sample Mendelian randomization (MR) study to elucidate the causal relationships between immune cells, inflammatory cytokines, plasma metabolites, and the risk of ED. Methods: Data on 91 inflammatory cytokines (n=14,736), 731 immune phenotypes (n=3,757) and 1,400 circulating metabolites (n=8,000) were obtained from genome-wide association studies (GWAS) as exposures, while ED data were sourced from the Integrative Epidemiology Unit (IEU) Open GWAS database (n=223,805) as outcomes. A two-sample MR analysis was performed to determine the relationships between exposures and outcomes. The inverse variance weighted (IVW) method was used as the primary MR analysis approach, supplemented by additional methods. Sensitivity analyses, including Cochran's Q test for heterogeneity and MR-Egger intercept for horizontal pleiotropy, were conducted to assess the robustness of the MR results. Results: At a significance level of P<0.01, we identified 12 factors associated with ED: five immune cells, one inflammatory cytokine, two metabolites, and four metabolite ratios. Specifically, CD19 on immunoglobulin D- (IgD-) CD38+ B cells [odds ratio (OR) =1.17; 95% confidence interval (CI): 1.06-1.30], CD4 on terminally differentiated CD4+ T cells (OR =1.07; 95% CI: 1.02-1.12), CD25 on IgD+ CD38dim B cells (OR =1.05; 95% CI: 1.01-1.09), CD25 on IgD+ CD24- B cells (OR =1.04; 95% CI: 1.01-1.07), and IgD on IgD+ B cells (OR =0.88; 95% CI: 0.79-0.97) were associated with ED. Among inflammatory cytokines, only elevated levels of urokinase-type plasminogen activator (uPA) significantly reduced the risk of ED (OR =0.83; 95% CI: 0.73-0.95). Six metabolites, including glycerol levels (OR =1.30; 95% CI: 1.08-1.56), aspartate to N-acetylglucosamine to N-acetylgalactosamine ratio (OR =1.21; 95% CI: 1.07-1.37), cholesterol to taurocholate ratio (OR =1.23; 95% CI: 1.07-1.42), 4-methyl-2-oxopentanoate to 3-methyl-2-oxobutyrate ratio (OR =1.26; 95% CI: 1.07-1.48), alpha-ketoglutarate to kynurenine ratio (OR =0.86; 95% CI: 0.76-0.96), and X-16964 levels (OR =1.24; 95% CI: 1.06-1.45) were significantly associated with ED. Sensitivity analyses did not reveal any heterogeneity or pleiotropy. Conclusions: Our MR analysis indicates that immune inflammation and metabolism have both inducing and protective effects on ED risk. These findings provide new insights for clinicians regarding the treatment and prevention of ED. Additionally, our study offers novel insights into the pathogenesis of ED. Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-395/coif). The authors have no conflicts of interest to declare. (2024 AME Publishing Company. All rights reserved.)
Databáze:	MEDLINE
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