Genes Variants and the Risk for Restless Legs Syndrome

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Dec 11

PMID 36499121

Authors

Felix Javier Jimenez-Jimenez

Javier Gomez-Tabales

Hortensia Alonso-Navarro

Christopher Rodriguez

Laura Turpin-Fenoll

Jorge Millan-Pascual

Ignacio Alvarez

Pau Pastor

Marisol Calleja

Rafael Garcia-Ruiz

Santiago Navarro-Munoz

Marta Recio-Bermejo

Jose Francisco Plaza-Nieto

Esteban Garcia-Albea

Elena Garcia-Martin

Jose A G Agundez

Affiliations

Soon will be listed here.

Abstract

According to several studies, inflammatory factors could be related to the pathogenesis of idiopathic restless legs syndrome (RLS). In addition, RLS and Parkinson's disease (PD) have shown a possible relationship, and recent studies have shown an association between rs1922452 and rs951818 single nucleotide variants (SNVs) and the risk for PD. For these reasons, we investigated the possible association between common variants in the genes (which encoded proteins involved in inflammatory and autoimmune responses) and the risk for RLS in a Caucasian Spanish population. We assessed the frequencies of rs1922452, rs951818, and rs870849 genotypes and allelic variants in 285 patients with idiopathic RLS and 350 healthy controls using a specific -based qPCR assay. We also analyzed the possible influence of the genotypes' frequencies on several variables, including age at onset of RLS, gender, family history of RLS, and response to drugs commonly used in the treatment of RLS. We found a lack of association between the frequencies of genotypes and allelic variants of the 3 SNVs studied and the risk of RLS, and a weak though significant association between the rs1922452 GG genotype and an older age at onset of RLS. With the exception of this association, our findings suggest that common SNVs in the genes are not associated with the risk of developing idiopathic RLS in Caucasian Spanish people.

References

Jimenez-Jimenez F, Gomez-Tabales J, Alonso-Navarro H, Zurdo M, Turpin-Fenoll L, Millan-Pascual J . Association Between the rs1229984 Polymorphism in the Alcohol Dehydrogenase 1B Gene and Risk for Restless Legs Syndrome. Sleep. 2017; 40(12). DOI: 10.1093/sleep/zsx174. View

Jimenez-Jimenez F, Alonso-Navarro H, Garcia-Martin E, Agundez J . Association between restless legs syndrome and peripheral neuropathy: A systematic review and meta-analysis. Eur J Neurol. 2021; 28(7):2423-2442. DOI: 10.1111/ene.14840. View

Hannier S, Tournier M, Bismuth G, Triebel F . CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling. J Immunol. 1998; 161(8):4058-65. View

Allen R, Picchietti D, Garcia-Borreguero D, Ondo W, Walters A, Winkelman J . Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria--history, rationale, description, and significance. Sleep Med. 2014; 15(8):860-73. DOI: 10.1016/j.sleep.2014.03.025. View

Guo W, Zhou M, Qiu J, Lin Y, Chen X, Huang S . Association of LAG3 genetic variation with an increased risk of PD in Chinese female population. J Neuroinflammation. 2019; 16(1):270. PMC: 6918662. DOI: 10.1186/s12974-019-1654-6. View

Jimenez-Jimenez F, Alonso-Navarro H, Martinez C, Zurdo M, Turpin-Fenoll L, Millan-Pascual J . Neuronal nitric oxide synthase (nNOS, NOS1) rs693534 and rs7977109 variants and risk for restless legs syndrome. J Neural Transm (Vienna). 2014; 122(6):819-23. DOI: 10.1007/s00702-014-1322-z. View

Trotti L, Rye D, De Staercke C, Hooper W, Quyyumi A, Bliwise D . Elevated C-reactive protein is associated with severe periodic leg movements of sleep in patients with restless legs syndrome. Brain Behav Immun. 2012; 26(8):1239-43. PMC: 3468666. DOI: 10.1016/j.bbi.2012.06.003. View

Roco A, Jimenez-Jimenez F, Alonso-Navarro H, Martinez C, Zurdo M, Turpin-Fenoll L . MAPT1 gene rs1052553 variant is unrelated with the risk for restless legs syndrome. J Neural Transm (Vienna). 2012; 120(3):463-7. DOI: 10.1007/s00702-012-0897-5. View

Garcia-Martin E, Jimenez-Jimenez F, Alonso-Navarro H, Martinez C, Zurdo M, Turpin-Fenoll L . Heme Oxygenase-1 and 2 Common Genetic Variants and Risk for Restless Legs Syndrome. Medicine (Baltimore). 2015; 94(34):e1448. PMC: 4602895. DOI: 10.1097/MD.0000000000001448. View

10.

Pfeffer C, Olsen B . Editorial: Journal of negative results in biomedicine. J Negat Results Biomed. 2002; 1:2. PMC: 149424. DOI: 10.1186/1477-5751-1-2. View

11.

Weinstock L, Walters A, Brook J, Kaleem Z, Afrin L, Molderings G . Restless legs syndrome is associated with mast cell activation syndrome. J Clin Sleep Med. 2020; 16(3):401-408. PMC: 7075100. DOI: 10.5664/jcsm.8216. View

12.

Jimenez-Jimenez F, Esguevillas G, Alonso-Navarro H, Zurdo M, Turpin-Fenoll L, Millan-Pascual J . Gamma-aminobutyric acid (GABA) receptors genes polymorphisms and risk for restless legs syndrome. Pharmacogenomics J. 2018; 18(4):565-577. DOI: 10.1038/s41397-018-0023-7. View

13.

Kitakata S, Furukawa S, Miyake T, Shiraishi K, Tange K, Hashimoto Y . Association between clinical outcomes and restless legs syndrome in Japanese patients with ulcerative colitis. J Sleep Res. 2022; 31(6):e13691. DOI: 10.1111/jsr.13691. View

14.

Jimenez-Jimenez F, Agundez B, Gomez-Tabales J, Alonso-Navarro H, Turpin-Fenoll L, Millan-Pascual J . Common Endothelial Nitric Oxide Synthase Single Nucleotide Polymorphisms are not Related With the Risk for Restless Legs Syndrome. Front Pharmacol. 2021; 12:618989. PMC: 7959806. DOI: 10.3389/fphar.2021.618989. View

15.

Ruffo E, Wu R, Bruno T, Workman C, Vignali D . Lymphocyte-activation gene 3 (LAG3): The next immune checkpoint receptor. Semin Immunol. 2019; 42:101305. PMC: 6920665. DOI: 10.1016/j.smim.2019.101305. View

16.

Buratti L, Petrelli C, Viticchi G, Provinciali L, Silvestrini M . Severe recurrent restless legs syndrome associated with systemic inflammation. Sleep Med. 2016; 29:90-91. DOI: 10.1016/j.sleep.2016.07.024. View

17.

Mewes C, Alexander T, Buttner B, Hinz J, Alpert A, Popov A . Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis-A Prospective Genetic Association Study. J Clin Med. 2021; 10(22). PMC: 8621793. DOI: 10.3390/jcm10225302. View

18.

Dowsett J, Didriksen M, von Stemann J, Larsen M, Thorner L, Sorensen E . Chronic inflammation markers and cytokine-specific autoantibodies in Danish blood donors with restless legs syndrome. Sci Rep. 2022; 12(1):1672. PMC: 8803845. DOI: 10.1038/s41598-022-05658-1. View

19.

Wang S, Zhang X, Leng S, Xu Q, Sheng Z, Zhang Y . Immune Checkpoint-Related Gene Polymorphisms Are Associated With Primary Immune Thrombocytopenia. Front Immunol. 2021; 11:615941. PMC: 7874092. DOI: 10.3389/fimmu.2020.615941. View

20.

Altman D, Bland J . Diagnostic tests 2: Predictive values. BMJ. 1994; 309(6947):102. PMC: 2540558. DOI: 10.1136/bmj.309.6947.102. View