Iron and The Restless Legs Syndrome

Sun, Erica R.; Chen, Clara A.; Ho, George; Earley, Christopher J.; Allen, Richard P.

doi:10.1093/sleep/21.4.381

Cited by 377 publications

(223 citation statements)

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“…Other retrospective studies with sample sizes between 27 and 302 RLS patients identified associations of serum ferritin to RLS severity and/ or the need for therapeutic augmentation. [22][23][24][25] Recently, low serum ferritin was described as a significant predictor of RLS in 301 hospital patients older 50 years of whom 55 had RLS. 26 On the other hand, cross-sectional studies on 365, 701, and 714 individuals from German, 2 Tyrolean, 3 and Korean 27 population cohorts with 36, 74, and 59 RLS cases, respectively, did not show an association to serum ferritin.…”

Section: Discussionmentioning

confidence: 99%

Dilution of candidates: the case of iron-related genes in restless legs syndrome

et al. 2012

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Restless legs syndrome (RLS) is a common multifactorial disease. Some genetic risk factors have been identified. RLS susceptibility also has been related to iron. We therefore asked whether known iron-related genes are candidates for association with RLS and, vice versa, whether known RLS-associated loci influence iron parameters in serum. RLS/control samples (n ¼ 954/1814 in the discovery step, 735/736 in replication 1, and 736/735 in replication 2) were tested for association with SNPs located within 4 Mb intervals surrounding each gene from a list of 111 iron-related genes using a discovery threshold of P ¼ 5 Â 10 À4 . Two population cohorts (KORA F3 and F4 with together n ¼ 3447) were tested for association of six known RLS loci with iron, ferritin, transferrin, transferrin-saturation, and soluble transferrin receptor. Results were negative. None of the candidate SNPs at the iron-related gene loci was confirmed significantly. An intronic SNP, rs2576036, of KATNAL2 at 18q21.1 was significant in the first (P ¼ 0.00085) but not in the second replication step (joint nominal P-value ¼ 0.044). Especially, rs1800652 (C282Y) in the HFE gene did not associate with RLS. Moreover, SNPs at the known RLS loci did not significantly affect serum iron parameters in the KORA cohorts. In conclusion, the correlation between RLS and iron parameters in serum may be weaker than assumed. Moreover, in a general power analysis, we show that genetic effects are diluted if they are transmitted via an intermediate trait to an end-phenotype. Sample size formulas are provided for small effect sizes. Keywords: restless legs syndrome; iron parameters; MEIS1 haplotype; power calculation; linear regression; logistic regression INTRODUCTIONRestless legs syndrome (RLS) 1 is a sensory-motor disorder characterized by an urge to move and unpleasant sensations in the lower limbs at rest. In Caucasians, RLS is present in up to 10% of the population. 2,3 Pregnancy, uremia, celiac disease, and iron deficiency are considered to be risk factors. 4 RLS also has a considerable heritability and is associated with multiple genetic risk factors. Genome-wide association studies 5-10 identified variants in six loci encompassing the genes MEIS1, BTBD9, MAP2K5/SKOR1, PTPRD, and TOX3/non-coding RNA.Aiming for the identification of further genetic risk factors of RLS, we addressed the apparent relation of RLS susceptibility to iron metabolism and iron availability 11 that has been explained by cerebral iron being crucial in the etiology of RLS. 12 We therefore tested the SNPs at the loci of a candidate set of genes known to be involved in iron metabolism for association with RLS. Vice versa, we asked whether RLS genes are involved in iron metabolism because the RLSassociated SNP rs3923809 at the BTBD9 locus has previously been reported to be associated with the serum level of ferritin in a study on RLS subjects and their relatives. 6

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Section: Discussionmentioning

confidence: 99%

Dilution of candidates: the case of iron-related genes in restless legs syndrome

et al. 2012

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“…Considering this finding and the absence of correlation of calcium and phosphorus concentration and the presence of RLS, as demonstrated by the present and previous studies 1, 9 , we consider that hyperparathyroidism is not an important factor in the development of the syndrome in CRF patients. It is well known that iron deficiency can play a role in the pathophysiology of the syndrome in patients without renal disease 14,15 . Our study, however, corroborates previous findings indicating that in CRF it is not significantly implicated in the mechanism of the disease 1,9 .…”

Section: Discussionmentioning

confidence: 99%

Restless legs syndrome in patients on chronic hemodialysis in a Brazilian city: frequency, biochemical findings and comorbidities

Filho

Gorini

Purysko

et al. 2003

Arq. Neuro-Psiquiatr.

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-Objective: To evaluate the frequency of restless legs syndrome (RLS) in patients with chronic renal failure (CRF) in Petrópolis, Brazil, and investigate associations between the syndrome and: demographic characteristics, biochemical variables and comorbidities. Method: A cross-sectional study in which we interviewed 176 patients on dialytic therapy based on criteria elaborated by the International Restless Legs Syndrome Study Group, and compared data of patients with and without RLS. Results: The frequency was 14.8 %. There were no significant differences between the two groups in demographic and biochemical variables investigated (iron, creatinine, intact parathyroid hormone, hemoglobin, calcium, phosphate). We found no association between RLS and the most common comorbidities, except for chronic glomerulonephritis (CGN) (OR = 3.84, p < 0.01). Conclusion: In the studied population RLS is a common disorder, and is not associated with the investigated biochemical abnormalities. A higher frequency of RLS in subjects with CGN is a finding that needs further investigation.KEY WORDS: restless legs syndrome, chronic renal failure, chronic glomerulonephritis.Síndrome das pernas inquietas em pacientes em programa de hemodiálise em P índrome das pernas inquietas em pacientes em programa de hemodiálise em P índrome das pernas inquietas em pacientes em programa de hemodiálise em P índrome das pernas inquietas em pacientes em programa de hemodiálise em P índrome das pernas inquietas em pacientes em programa de hemodiálise em Petrópolis, RJ: frequência, etrópolis, RJ: frequência, etrópolis, RJ: frequência, etrópolis, RJ: frequência, etrópolis, RJ: frequência, aspectos laboratoriais e comorbidades. aspectos laboratoriais e comorbidades. aspectos laboratoriais e comorbidades. aspectos laboratoriais e comorbidades. aspectos laboratoriais e comorbidades. RESUMO -Objetivo: Determinar a frequência de síndrome das pernas inquietas (SPI) em pacientes com insuficiência renal crônica (IRC) em Petrópolis, Brasil, e investigar associação entre a síndrome e: dados demográficos, achados bioquímicos e comorbidades. Método: Estudo transversal no qual entrevistamos 176 pacientes em terapia dialítica a partir de critérios definidos pelo International Restless Legs Syndrome Study Group, e comparamos dados de pacientes com e sem SPI. Resultado: A frequência foi 14,8 %. Não houve diferença significativa entre os 2 grupos nas variáveis demográficas e bioquímicas (ferro, cretinina, paratormônio, hemoglobina, cálcio, fósforo) investigadas. Não houve associação entre SPI e as principais comorbidades, exceto glomerulonefrite crônica (GNC) (OR = 3,84, p < 0,01). Conclusão: SPI é condição comum na população estudada, e não é associada com as alterações bioquímicas investigadas. O achado de maior frequência de SPI em pacientes com GNC merece investigações mais detalhadas. The frequency of restless legs syndrome (RLS) is higher in patients with end-stage renal disease than in the general population, and previous studies have reported it to vary...

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“…Serum ferritin below 50 mcg/L has been associated with severity of RLS in adult studies [104][105][106] and has been proposed as a mechanism in pediatrics [100,107]. There is some evidence of low iron stores in at least some children with RLS (ferritin below 50 mcg/L in 83-89 % and less than median for age and gender in 72-75 %) [108,109] though no systematic studies have been completed.…”

Section: Restless Legs Syndrome (Rls)mentioning

confidence: 99%

Current Treatment of Selected Pediatric Sleep Disorders

Sullivan

2012

Neurotherapeutics

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While pediatric sleep disorders are relatively common, treatments are often not straightforward. There is often a paucity of gold standard studies and data available to guide clinicians, treatments may yield arguably incomplete results, interventions may require chronic use, and/ or involve multiple modalities including behavioral interventions that require high parental and family commitment. This review points out diagnostic differences compared to adults and focuses on current therapy for selected common pediatric sleep disorders including sleep disordered breathing/ obstructive sleep apnea, narcolepsy, and restless legs syndrome. Other common pediatric sleep disorders, such as insomnia and parasomnias, are not covered.

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Iron and The Restless Legs Syndrome

Cited by 377 publications

References 0 publications

Dilution of candidates: the case of iron-related genes in restless legs syndrome

Dilution of candidates: the case of iron-related genes in restless legs syndrome

Restless legs syndrome in patients on chronic hemodialysis in a Brazilian city: frequency, biochemical findings and comorbidities

Current Treatment of Selected Pediatric Sleep Disorders

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