RESUMEN
The possible role of gammaaminobutyric acid (GABA) in the pathophysiology of restless legs syndrome (RLS) is suggested by the symptomatic improvement achieved with GABAergic drugs. Thalamic GABA levels have shown positive correlation with periodic limb movements indices and with RLS severity. We tried to investigate the possible association between the most common single nucleotide polymorphisms (SNPs) in the GABA receptors (GABR) genes rho1, 2, and 3 (GABRR1, GABRR2, GABRR3), alpha4 (GABRA4), epsilon (GABRE), and theta (GABRQ) with the risk of developing RLS. We studied the genotype and allelic variant frequencies of the most common SNPs in the GABRR1(rs12200969, rs1186902), GABRR2(rs282129), GABRR3(rs832032), GABRA4(rs2229940), GABRE(rs1139916), and GABRQ(rs3810651) genes in 205 RLS patients and 230 age- and gender-matched healthy controls using specific TaqMan assays. The frequencies of the GABRR3 rs832032TT genotype and the allelic variant GABRR3 rs832032T were significantly higher in RLS patients than in controls (odds ratio [95% confidence intervals] 7.08[1.48-46.44] and 1.66[1.16-2.37], respectively), although only the higher frequency of the rs832032T allele remained as significant after multiple comparison analysis, both in the whole series and in the female gender. The frequencies of the other genotypes of allelic variants did not differ significantly between RLS patients and controls. RLS patients carrying the GABRA4 rs2229940TT genotype showed a significantly younger age at onset of RLS symptoms than those with the other two genotypes. These results suggest association between GABRR3rs832032 polymorphism and the risk for RLS, and a modifier effect of GABRA4 rs2229940 on the age of onset of RLS.
Asunto(s)
Predisposición Genética a la Enfermedad , Receptores de GABA-A/genética , Síndrome de las Piernas Inquietas/genética , Adulto , Edad de Inicio , Anciano , Alelos , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Receptores de GABA/genética , Síndrome de las Piernas Inquietas/fisiopatología , Factores de RiesgoRESUMEN
A recent meta-analysis suggests an association between the rs11558538 single nucleotide polymorphism in the histamine-N-methyl-transferase (HNMT) gene and the risk for Parkinson's disease. Based on the possible relationship between PD and restless legs syndrome (RLS), we tried to establish whether rs11558538 SNP is associated with the risk for RLS. We studied the genotype and allelic variant frequencies of HNMT rs11558538 SNP 205 RLS patients and 410 healthy controls using a TaqMan assay. The frequencies of the HNMT rs11558538 genotypes allelic variants were similar between RLS patients and controls, and were not influenced by gender, family history of RLS, or RLS severity. RLS patients carrying the genotype rs11558538TT had an earlier age at onset, but this finding was based on three subjects only. These results suggest a lack of major association between HNMT rs11558538 SNP and the risk for RLS.
Asunto(s)
Histamina N-Metiltransferasa/genética , Polimorfismo de Nucleótido Simple , Síndrome de las Piernas Inquietas/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , Masculino , Persona de Mediana Edad , Síndrome de las Piernas Inquietas/epidemiología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Adulto JovenRESUMEN
Several biochemical, neuropathological, and experimental data suggest a possible role of nitric oxide (NO) in the pathophysiology of restless legs syndrome (RLS). Two single nucleotide polymorphisms (SNPs) neuronal nitric oxide synthase (nNOS or NOS1) gene (rs7977109 and rs693534) have been found to be associated with the risk for RLS in Germans, although only one of them (rs7977109) remained as significant after multiple comparison tests. The aim of our study was to replicate the possible association between these SNPs and risk for RLS in the Spanish population. We studied the allelic and genotype frequencies of the SNPs rs7977109 and rs693534 in 205 patients with RLS and 328 healthy controls using TaqMan genotyping. The rs7977109 and rs693534 genotypes and allelic frequencies did not significantly differ between patients with RLS and controls and were unrelated with the age at onset of RLS, gender, ferritin levels, and response to dopaminergic or gabaergic agents. The rs7999109GA genotype was overrepresented in RLS patients with positive family history of RLS, and in patients with symptomatic response to clonazepam. The results of our study suggest that these two NOS1 SNPs are not related to the overall risk for RLS in the Spanish population.
Asunto(s)
Predisposición Genética a la Enfermedad , Óxido Nítrico Sintasa de Tipo I/genética , Polimorfismo de Nucleótido Simple , Síndrome de las Piernas Inquietas/genética , Estudios de Cohortes , Femenino , Frecuencia de los Genes , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad , Síndrome de las Piernas Inquietas/epidemiología , RiesgoRESUMEN
Mutations in the microtubule-associated protein tau gene (MAPT) can cause frontotemporal dementia with Parkinsonism linked to the chromosome 17, and are associated with the risk for progressive supranuclear palsy, Parkinson's disease, corticobasal degeneration, and multiple system atrophy. We tried to establish, whether MAPT H1 discriminating haplotype single nucleotide polymorphisms (SNP) (rs1052553) is associated with the risk for restless legs syndrome (RLS). We studied the allelic and genotype frequencies of the SNP rs1052553 in 205 patients with RLS and 324 healthy controls using TaqMan genotyping. rs1052553 genotype and allelic frequencies did not differ significantly between patients with RLS and controls, and were unrelated with the age at onset of RLS, gender, family history of RLS, and severity of RLS. The results of the present study suggest that the SNP rs1052553 is not related with the risk for RLS.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Síndrome de las Piernas Inquietas/genética , Proteínas tau/genética , Adulto , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Factores de RiesgoRESUMEN
Early recognition of psychopathological symptoms (PSs) after stroke is important because they greatly influence the recovery of patients. The aim of this study was to investigate the predictive factors of PSs occurring in patients with ischemic stroke. Eighty-nine patients were prospectively evaluated upon admission and 4, 12, and 26 weeks later with the Neuropsychiatric Inventory, Hamilton's Rating Scales for Depression and Anxiety, and a battery of neuropsychological and functional scales. Depression and apathy were the most frequent PSs detected after stroke. Premorbid psychopathologies and right-hemisphere location were the main predictive indicators of early and long-term PSs.
Asunto(s)
Síntomas Conductuales/etiología , Síntomas Conductuales/patología , Trastornos Mentales/etiología , Accidente Cerebrovascular/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Estadística como Asunto , Factores de TiempoRESUMEN
Background/Objectives: Several studies have raised the possibility of an association between alcohol consumption and the risk of developing restless legs syndrome (RLS). Moreover, an important percentage of patients under alcohol detoxification therapy develop RLS symptoms that fulfil the criteria for idiopathic RLS during alcohol withdrawal. We have aimed to establish the possible association between two common single nucleotide polymorphisms (SNPs) in the alcohol-dehydrogenase 1B (ADH1B) gene and the risk for RLS. Methods: We studied, using specific TaqMan assays, the genotype and allelic variant frequencies of ADH1B rs1229984 and ADH1B rs6413413 SNPs in 205 RLS patients and 505 gender-matched healthy controls. Results: The sum of the frequencies of rs1229984CT and rs1229984TT genotypes, as well as the frequency of the rs1229984T allelic variant, was significantly higher in RLS patients than in controls, both in the whole group and in females. The frequencies of genotypes and allelic variants of the rs6413413 SNP were similar between the two groups. RLS patients with the rs1229984CT genotype were younger, and those with the rs122984TT genotype older, at onset of RLS symptoms than those with the rs1229984CC genotype. None of the studied SNPs were related either with positivity of family history for RLS or with RLS severity. Conclusions: These results suggest an association between rs1229984 SNP and the risk for RLS.
Asunto(s)
Alcohol Deshidrogenasa/genética , Estudios de Asociación Genética/métodos , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Síndrome de las Piernas Inquietas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/genética , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Síndrome de las Piernas Inquietas/diagnóstico , Síndrome de las Piernas Inquietas/epidemiología , Factores de Riesgo , Adulto JovenRESUMEN
Several neurochemical, neuropathological, neuroimaging, and experimental data, suggest that iron deficiency plays an important role in the pathophysiology of restless legs syndrome (RLS). Heme-oxygenases (HMOX) are an important defensive mechanism against oxidative stress, mainly through the degradation of heme to biliverdin, free iron, and carbon monoxide. We analyzed whether HMOX1 and HMOX2 genes are related with the risk to develop RLS.We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations (CNVs) of these genes in 205 subjects RLS and 445 healthy controls.The frequencies of rs2071746TT genotype and rs2071746T allelic variant were significantly lower in RLS patients than that in controls, although the other 3 studied SNPs did not differ between RLS patients and controls. None of the studied polymorphisms influenced the disease onset, severity of RLS, family history of RLS, serum ferritin levels, or response to dopaminergic agonist, clonazepam or GABAergic drugs.The present study suggests a weak association between HMOX1 rs2071746 polymorphism and the risk to develop RLS in the Spanish population.
Asunto(s)
Variación Genética , Hemo-Oxigenasa 1/genética , Polimorfismo de Nucleótido Simple , Síndrome de las Piernas Inquietas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
Several recent works suggest a possible role of vitamin D deficiency in the etiology or restless legs syndrome (RLS). We analyzed the possible relationship of 2 common single nucleotide polymorphisms (SNPs) in the vitamin D3 receptor (VDR) gene with the risk for RLS.We studied the genotype and allelic variant frequencies of VDR rs2228570 and VDR rs731236 SNPs in 205 RLS patients and 445 healthy controls using a TaqMan essay.The frequencies of the rs731236AA genotype and the allelic variant rs731236A were significantly lower in RLS patients than in controls (P < 0.005 and < 0.01, respectively). Restless legs syndrome patients carrying the allelic variant rs731236G had an earlier age at onset, and those carrying the rs731236GG genotype had higher severity of RLS, although these data disappeared after multivariate analyses. None of the SNPs studied was related with the positivity of family history of RLS.These results suggest a modest, but significant association between VDR rs731236 SNP and the risk for RLS.
Asunto(s)
Receptores de Calcitriol/genética , Síndrome de las Piernas Inquietas/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Población BlancaRESUMEN
OBJECTIVE: A glutamatergic dysfunction has been postulated to play a role in restless legs syndrome (RLS) pathophysiology, as glutamate concentrations have been found to increase in the thalamus of RLS patients. The aim of our study was to investigate the possible association between the single nucleotide polymorphism (SNP) rs3794087 in the solute carrier family 1 (glial high affinity glutamate transporter), member 2 gene, SLC1A2, related with glutamate transport and the risk for RLS. METHODS: We studied the allelic and genotype frequencies of the SNP rs3794087 in 205 patients with RLS and 328 healthy controls using TaqMan genotyping. RESULTS: The rs3794087 genotype and allelic frequencies did not significantly differ between patients with RLS and controls and were unrelated with the age at onset of RLS, gender, and family history of RLS. CONCLUSIONS: The results of our study suggest that the rs3794087 polymorphism is not related to the risk for RLS.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Proteínas de Transporte de Glutamato en la Membrana Plasmática/genética , Polimorfismo de Nucleótido Simple/genética , Síndrome de las Piernas Inquietas/genética , Adulto , Alelos , Transportador 2 de Aminoácidos Excitadores , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Masculino , Factores de RiesgoRESUMEN
We describe the clinical phenotype of nine kindred with presenile Alzheimer's disease (AD) caused by different presenilin 1 (PS1) point mutations, and compare them with reported families with mutations in the same codons. Mutations were in exon 4 (Phe105Val), exon 5 (Pro117Arg, Glu120Gly), exon 6 (His163Arg), exon 7 (Leu226Phe), exon 8 (Val261Leu, Val272Ala, Leu282Arg), and exon 12 (Ile439Ser). Three of these amino acid changes (Phe105Val, Glu120Gly, and Ile439Ser) had not been previously reported. Distinct clinical features, including age of onset, symptoms and signs associated with the cortical-type dementia and aggressiveness of the disease, characterized the different mutations and were quite homogeneous across family members. Age of onset fell within a consistent range: some mutations caused the disease in the thirties (P117R, L226F, V272A), other in the forties (E120G, H163R, V261L, L282R), and other in the fifties (F105V, I439S). Associated features also segregated with specific mutations: early epileptic activity (E120G), spastic paraparesis (V261L), subcortical dementia and parkinsonism (V272A), early language impairment, frontal signs, and myoclonus (L226F), and late myoclonus and seizures (H163R, L282R). Neurological deterioration was particularly aggressive in PS1 mutations with earlier age of onset such as P117R, L226F, and E120G. With few exceptions, a similar clinical phenotype was found in families reported to have either the same mutation or different amino acid changes in the same codons. This series points to a strong influence of the specific genetic defect in the development of the clinical phenotype.