Inflammatory markers and the risk of idiopathic sudden sensorineural hearing loss: A Mendelian randomization study

Tingfeng Zhou; Mengjiao Chen; Ziyi Yuan; Zhigang Xia; Shurou Zhang; Ziheng Zhang; Huanqi Chen; Renyu Lin

doi:10.3389/fneur.2023.1111255

Inflammatory markers and the risk of idiopathic sudden sensorineural hearing loss: A Mendelian randomization study

Front Neurol. 2023 Feb 22:14:1111255. doi: 10.3389/fneur.2023.1111255. eCollection 2023.

Authors

Tingfeng Zhou¹, Mengjiao Chen¹, Ziyi Yuan², Zhigang Xia¹, Shurou Zhang¹, Ziheng Zhang¹, Huanqi Chen¹, Renyu Lin¹

Affiliations

¹ Department of Otolaryngology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Wenzhou Medical University, Wenzhou, China.

Abstract

Background: Observational studies suggest that inflammatory markers may increase the risk of idiopathic sudden sensorineural hearing loss (ISSHL). However, the causal relationship between the two has not been established. We sought to assess the possible causal effect between several genetically predicted inflammatory markers and ISSHL by Mendelian random (MR) analysis.

Methods: We extracted single nucleotide polymorphisms (SNPs) associated with C-reactive protein (CRP), Tumor necrosis factor-α (TNF-α), and fibrinogen from abstract data from the European Individual Large genome-wide association studies (GWAS). Genetic data for ISSHL were obtained from the FinnGen study (n = 196,592). Effect estimates were assessed using inverse variance weighting (IVW) as the primary method. Sensitivity analyses were performed using weighted median, MR-Egger, and MR-PRESSO to evaluate heterogeneity and pleiotropy.

Results: In the random-effects IVW approach, there was a significant causal relationship between genetic susceptibility to CRP levels and ISSHL (OR = 1.23, 95% CI = 1.02-1.49, P = 0.03). In contrast, genetic TNF-α and fibrinogen were not risked factors for ISSHL (OR = 1.14, 95% CI = 0.88-1.49, P = 0.30; OR = 0.74, 95% CI = 0.07-7.96, P = 0.30; OR = 1.05, 95% CI = 0.88-1.25, P = 0.59). All the above results were consistent after validation by different Mendelian randomization methods and sensitivity analyses.

Conclusion: This Mendelian randomization study provides causal evidence that CRP is a risk factor for ISSHL, while TNF-α and fibrinogen do not increase the risk for ISSHL Introduction.

Keywords: C-reactive protein; Mendelian randomization; TNF-α; fibrinogen; idiopathic sudden sensorineural hearing loss; inflammation.

Grants and funding

This work was supported by the Natural Science Foundation of Zhejiang Province, China (LY19H130001), Basic public welfare scientific research project of Wenzhou Science, and Technology Bureau (Y20210313).