A Potential Role for Zinc in Restless Legs Syndrome

Overview

Journal Sleep

Publisher Oxford University Press

Specialty Psychiatry

Date 2020 Nov 11

PMID 33175142

Citations 5

Authors

Pan Chen

Julia Bornhorst

Stephanie Patton

Kanika Bagai

Rachana Nitin

Mahfuzur Miah

Dominic J Hare

Kai Kysenius

Peter J Crouch

Lan Xiong

Guy A Rouleau

Tanja Schwerdtle

James Connor

Michael Aschner

Aaron B Bowman

Arthur S Walters

Affiliations

Soon will be listed here.

Abstract

Study Objectives: Evaluate serum and brain noniron metals in the pathology and genetics of restless legs syndrome (RLS).

Methods: In two independent studies (cohorts 1 and 2), in which subjects either remained on medications or tapered off medications, we analyzed serum levels of iron, calcium, magnesium, manganese, copper, and zinc both in RLS patients and controls, and assessed the prevalence of the MEIS1 and BTBD9 risk alleles previously established through genome-wide association studies. Human brain sections and a nematode genetic model were also quantified for metal levels using mass spectrometry.

Results: We found a significant enrichment for the BTBD9 risk genotype in the RLS affected group compared to control (p = 0.0252), consistent with previous literature. Serum (p = 0.0458 and p = 0.0139 for study cohorts 1 and 2, respectively) and brain (p = 0.0413) zinc levels were significantly elevated in the RLS patients versus control subjects.

Conclusion: We show for the first time that serum and brain levels of zinc are elevated in RLS. Further, we confirm the BTBD9 genetic risk factor in a new population, although the zinc changes were not significantly associated with risk genotypes. Zinc and iron homeostasis are interrelated, and zinc biology impacts neurotransmitter systems previously linked to RLS. Given the modest albeit statistically significant increase in serum zinc of ~20%, and the lack of association with two known genetic risk factors, zinc may not represent a primary etiology for the syndrome. Further investigation into the pathogenetic role that zinc may play in restless legs syndrome is needed.

Citing Articles

Sleep duration mediates the association between heavy metals and the prevalence of depression: an integrated approach from the NHANES (2005-2020).

Mao Q, Zhu X, Kong Y Front Psychiatry. 2024; 15:1455896.

PMID: 39286395 PMC: 11404323. DOI: 10.3389/fpsyt.2024.1455896.

Correlates of Restless Legs Syndrome in Older People.

Szklarek M, Kostka T, Kostka J J Clin Med. 2024; 13(5).

PMID: 38592261 PMC: 10932329. DOI: 10.3390/jcm13051364.

Review of the role of the endogenous opioid and melanocortin systems in the restless legs syndrome.

Walters A, Li Y, Koo B, Ondo W, Weinstock L, Champion D Brain. 2023; 147(1):26-38.

PMID: 37633259 PMC: 10796165. DOI: 10.1093/brain/awad283.

Serum Trace Elements Concentrations in Patients with Restless Legs Syndrome.

Jimenez-Jimenez F, Ayuso P, Alonso-Navarro H, Calleja M, Diez-Fairen M, Alvarez I Antioxidants (Basel). 2022; 11(2).

PMID: 35204155 PMC: 8868060. DOI: 10.3390/antiox11020272.

BTBD9 attenuates manganese-induced oxidative stress and neurotoxicity by regulating insulin growth factor signaling pathway.

Chen P, Cheng H, Zheng F, Li S, Bornhorst J, Yang B Hum Mol Genet. 2022; 31(13):2207-2222.

PMID: 35134179 PMC: 9262395. DOI: 10.1093/hmg/ddac025.

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