Inflammatory cytokine profiles in erectile dysfunction: a bidirectional Mendelian randomization

• Published in: Frontiers in immunology Vol. 15; p. 1342658
• Main Authors: Liu, Dongze, Qin, Zheng, Yi, Bocun, Xie, Hongbo, Liang, Yunan, Zhu, Liang, Yang, Kuo, Zhang, Hongtuan
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2024
• Subjects: bidirectional Mendelian randomization; Chemokine CXCL10 - genetics; Cytokines - genetics; erectile dysfunction; Erectile Dysfunction - genetics; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; IL-1ra; Inflammation Mediators - metabolism; inflammatory cytokine; IP-10; Male; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; bidirectional Mendelian randomization; inflammatory cytokine; IL-1ra; IP-10; erectile dysfunction
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1342658

Inflammatory cytokines (ICs) play an important role in erectile dysfunction (ED). Previous studies have demonstrated that most ED patients have high levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). The causality between 41 ICs and ED is investigated using the Mendelian randomization (MR) approach. Single nucleotide polymorphisms (SNPs) exposure data of 41 ICs came from a genome-wide association study (GWAS) of 8293 subjects. At the same time, the FINNGEN R9 database provided the ED outcome data containing 2205 ED patients and 164104 controls. MR-Egger (ME), inverse variance weighting (IVW), and weighted median (WM) were applied to conduct the MR study and IVW was taken as the main criterion. From a genetic perspective, the increase of interferon-inducible protein-10 (IP-10) level significantly increased the risk of ED (P=0.043, odds ratio (OR)=1.269, 95% confidence interval (95%CI): 1.007-1.600), while the increase of interleukin-1 receptor antagonist (IL-1RA) markedly decreased the risk of ED (P=0.037, OR=0.768, 95%CI: 0.600-0.984). Meanwhile, IP-10 (p=0.099) and IL-1RA (p=0.135) failed to demonstrate causality in reverse MR analysis. Changes in ICs levels will significantly affect the risk of ED, especially IP-10 as a risk component for ED and IL-1RA as a protective component for ED. In the future, we can achieve targeted treatment and prevention of ED by intervening with specific inflammatory factors.