Thr105Ile (rs11558538) polymorphism in the histamine-1-methyl-transferase (HNMT) gene and risk for restless legs syndrome

Jiménez‐Jiménez, Félix Javier; García‐Martín, Elena; Alonso‐Navarro, Hortensia; Martı́nez, Carmen; Zurdo, Martín; Turpín-Fenoll, Laura; Millán-Pascual, Jorge; Adeva-Bartolomé, Teresa; Cubo, Esther; Navacerrada, Francisco; Rojo-Sebastián, Ana; Rubio, Lluisa; Ortega‐Cubero, Sara; Pástor, Pau; Calleja, Marisol; Plaza-Nieto, José Francisco; Pilo‐de‐la‐Fuente, Belén; Arroyo-Solera, Margarita; E, García-Albea; Agúndez, José A. G.

doi:10.1007/s00702-016-1645-z

Cited by 17 publications

(5 citation statements)

References 34 publications

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“…A total of 285 patients with idiopathic RLS (iRLS), according to the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria [ 2 ], and 350 age- and sex-matched healthy controls were involved in this study. Approximately 60 percent of patients included in the current study had participated in case-control genetic association studies previously reported by our group [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. The inclusion of patients with iRLS implied the prior exclusion of all those with causes of secondary RLS, as described in detail elsewhere [ 48 ].…”

Section: Methodsmentioning

confidence: 99%

LAG3/CD4 Genes Variants and the Risk for Restless Legs Syndrome

Jiménez‐Jiménez

Gómez-Tabales

Alonso‐Navarro

et al. 2022

IJMS

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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 CD4 rs1922452 and CD4 rs951818 single nucleotide variants (SNVs) and the risk for PD. For these reasons, we investigated the possible association between common variants in the LAG3/CD4 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 CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants in 285 patients with idiopathic RLS and 350 healthy controls using a specific TaqMan-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 CD4 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 CD4/LAG3 genes are not associated with the risk of developing idiopathic RLS in Caucasian Spanish people.

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Section: Methodsmentioning

confidence: 99%

LAG3/CD4 Genes Variants and the Risk for Restless Legs Syndrome

Jiménez‐Jiménez

Gómez-Tabales

Alonso‐Navarro

et al. 2022

IJMS

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“…RLS patients were recruited from the Movement Disorders Unit of 4 hospitals, and healthy controls (none of them have personal or familial history of RLS, tremor, or other movement disorders) were staff or students from the University of Extremadura. Sixty percent of RLS patients were involved in other case-control genetic association studies published by our group (Jiménez-Jiménez et al, 2013;Roco et al, 2013;Jiménez-Jiménez et al, 2014;García-Martín et al, 2015;Jiménez-Jiménez et al, 2015a;Jiménez-Jiménez et al, 2015b;Jiménez-Jiménez et al, 2017a;Jiménez-Jiménez et al, 2017b;Jiménez-Jiménez et al, 2018b).…”

Section: Patients and Controlsmentioning

confidence: 99%

Common Endothelial Nitric Oxide Synthase Single Nucleotide Polymorphisms are not Related With the Risk for Restless Legs Syndrome

Jiménez‐Jiménez

Agúndez²,

Gómez-Tabales³

et al. 2021

Front. Pharmacol.

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Because nitric oxide and endothelial dysfunction could play a role in the pathogenesis of idiopathic restless legs syndrome (RLS), as was suggested by some preliminary data, we investigated the possible association between the rs2070744 variants in the endothelial nitric oxide synthase (eNOS or NOS3) gene (chromosome 7q36.1) and the risk for RLS in a Caucasian Spanish population. We assessed the frequencies of NOS3 single nucleotide polymorphisms (SNPs) rs2070744, rs1799983, and rs79467411 genotypes and allelic variants in 273 patients with idiopathic RLS and 325 healthy controls using a TaqMan-based qPCR assay. We also analyzed the possible influence of genotype frequency on age at onset of RLS symptoms, gender, family history of RLS, and response to drugs commonly used in the treatment of RLS such as dopaminergic drugs, clonazepam, and GABAergic drugs. The frequencies of genotypes and allelic variants were not associated with the risk for RLS and were not influenced by gender, age, and positive family history of RLS. We identified weak statistical associations of the SNP rs1799983 with the response to dopamine agonists (Pc = 0.018 for the rs1799983 G/T genotype) and of the SNP rs79467411 with the response to clonazepam (Pc = 0.018 for the rs79467411 G allele), although these findings should be cautiously interpreted and require further confirmation. These associations aside, our findings suggest that common NOS3 SNPs are not associated with the risk for idiopathic RLS in Caucasian Spanish people.

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“…The 3D location is shown in Figure 5A and Figure 5B. The variant was positioned in the α-helix, where its side chain hydroxyl formed two hydrogen bonds with a backbone oxygen after mutation, causing a marked decrease in the levels of both HNMT enzymatic activity and immunoreactive protein [26,27]. HNMT is an enzyme that has been implicated in neurotransmission by inactivating histamine in the central nervous system [28].…”

Section: Protein Structure and Characterization Of Missense Hnmt Mutationsmentioning

confidence: 99%

Integrated Transcriptome-wide Profiling and Protein Structure Analysis of Pathogenic Genes in Venous Thromboembolism

Ding

Zhang²,

Cao³

2021

Preprint

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BackgroundGenetic factors are considered to determine the balance of the coagulation and anticoagulation processes, yet the genetic variants related to venous thromboembolism (VTE) remain unclear. This study aimed to investigate the potential molecular mechanisms and pathogenic mutations associated with VTE by determining VTE-related differentially expressed genes (DEGs) by transcriptome-wide profiling and assaying protein structure in VTE.MethodsTwo gene expression datasets, GSE48000 and GSE19151, were accessed from the Gene Expression Omnibus (GEO) database to obtain gene expression data associated with VTE. We identified the DEGs between VTE patients and healthy people using R and performed functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, whole-exome sequencing (WES) was performed for 25 VTE patients and 17 normal cases, and the structural locations of pathogenic missense mutations were identified using pyMOL. Finally, DGIdb database was used to select candidate drugs for the treatment of VTE.ResultsA total of 232 DEGs were identified from the GEO database. The significant function of these DEGs was mostly involved in RNA catabolic process and ribosome pathway. Notably, the results of WES for DEGs and protein structure analysis showed that Histamine N-Methyltransferase (HNMT) (chr2: 138759649 C>T, rs11558538) may be a main predisposing factor for VTE. In addition, Amodiaquine, Harmaline, Aspirin, Metoprine, Dabigatran, and Diphenhydramine were screened for VTE therapy.ConclusionThe results showed that HNMT (chr2: 138759649 C>T, rs11558538) may be potential target for the diagnosis and treatment of VTE.

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Thr105Ile (rs11558538) polymorphism in the histamine-1-methyl-transferase (HNMT) gene and risk for restless legs syndrome

Cited by 17 publications

References 34 publications

LAG3/CD4 Genes Variants and the Risk for Restless Legs Syndrome

LAG3/CD4 Genes Variants and the Risk for Restless Legs Syndrome

Common Endothelial Nitric Oxide Synthase Single Nucleotide Polymorphisms are not Related With the Risk for Restless Legs Syndrome

Integrated Transcriptome-wide Profiling and Protein Structure Analysis of Pathogenic Genes in Venous Thromboembolism

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