Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 10:13:1088557.
doi: 10.3389/fendo.2022.1088557. eCollection 2022.

Genetic variation reveals the influence of steroid hormones on the risk of retinal neurodegenerative diseases

Kangcheng Liu  1 , Huimin Fan  1 , Hanying Hu  1 , Yanhua Cheng  1 , Jingying Liu  1 , Zhipeng You  1
Affiliations

Genetic variation reveals the influence of steroid hormones on the risk of retinal neurodegenerative diseases

Kangcheng Liu et al. Front Endocrinol (Lausanne). .

Abstract

It is difficult to get evidence from randomized trials of a causal relationship between steroid hormones produced by the adrenal gland and gonad and retinal neurodegenerative disorders (RND). In this study, genetic variations of aldosterone (Aldo), androstenedione (A4), progesterone (P4), hydroxyprogesterone (17-OHP), and testosterone/17β-estradiol (T/E2) were obtained from genome-wide association studies as instrumental variables. Mendelian randomization (MR) analysis was used to assess the impact on the risk of RND, including glaucoma (8,591 cases and 210,201 controls), diabetic retinopathy (DR, 14,584 cases and 202,082 controls) and age-related macular degeneration (AMD, 14,034 cases and 91,214 controls). As the main method, inverse variance weighted results suggest that the increased glaucoma risk was affected by T/E2 (OR = 1.11, 95% CI, 1.01-1.22, P = 0.03), which was further validated by other methods (PWM = 0.03, PMLE = 0.03, PMR-RAPS = 0.03). In the replicated stage, the causal relationship between T/E2 and glaucoma was verified based on the MRC-IEU consortium (P = 0.04). No impact of Aldo, A4, P4, 17-OHP, and T/E2 was observed for the risk of DR (P > 0.05) and AMD (P > 0.05). The heterogeneity test (P > 0.05) and pleiotropy test (P > 0.05) verified the robustness of the results. Our results suggest that T/E2 has a suggestive effect on the glaucoma risk. However, the genetic evidence based on a large sample does not support the effect of steroid hormones on DR and AMD risk. Further studies are vital to assess the possibility of steroid hormones as targets for prevention and treatment.

Keywords: Mendelian randomization; causality; glaucoma; retinal neurodegenerative disease; steroid hormones.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Assumptions of Mendelian randomization analysis between steroid hormone and RND.
Figure 2
Figure 2
Causal analysis of steroid hormone and RND based on MR analyses and sensitivity analyses in the discovery stage.
Figure 3
Figure 3
Causal analysis of steroid hormone and glaucoma based on MR analyses and sensitivity analyses in the replicated stage.
See this image and copyright information in PMC

References

    1. Holst JP, Soldin OP, Guo T, Soldin SJ. Steroid hormones: relevance and measurement in the clinical laboratory. Clin Lab Med (2004) 24:105–18. doi: 10.1016/j.cll.2004.01.004 - DOI - PMC - PubMed
    1. Sanderson JT. The steroid hormone biosynthesis pathway as a target for endocrine-disrupting chemicals. Toxicol Sci (2006) 94:3–21. doi: 10.1093/toxsci/kfl051 - DOI - PubMed
    1. Cascio C, Deidda I, Russo D, Guarneri P. The estrogenic retina: The potential contribution to healthy aging and age-related neurodegenerative diseases of the retina. Steroids (2015) 103:31–41. doi: 10.1016/j.steroids.2015.08.002 - DOI - PubMed
    1. Jain A, Wordinger RJ, Yorio T, Clark AF. Role of the alternatively spliced glucocorticoid receptor isoform GRβ in steroid responsiveness and glaucoma. J ocular Pharmacol Ther (2014) 30:121–7. doi: 10.1089/jop.2013.0239 - DOI - PMC - PubMed
    1. Fourgeux C, Bron A, Acar N, Creuzot-Garcher C, Bretillon L. 24S-hydroxycholesterol and cholesterol-24S-hydroxylase (CYP46A1) in the retina: from cholesterol homeostasis to pathophysiology of glaucoma. Chem Phys Lipids (2011) 164:496–9. doi: 10.1016/j.chemphyslip.2011.04.006 - DOI - PubMed

Publication types