Altered iron metabolism in lymphocytes from subjects with restless legs syndrome

OBJECTIVE: Studies using cerebrospinal fluid, magnetic resonance imaging, and autopsy tissue have implicated a primary role for brain iron insufficiency in restless legs syndrome (RLS). If the abnormalities of brain iron regulation reflect a basic disturbance of iron metabolism, then this might be expressed at least partially in some peripheral systems. Thus the study aim was to determine whether patients with RLS and control subjects show differences in lymphocyte iron regulator proteins. METHODS: Fasting morning blood samples were used to obtain common serum measures of iron status and to determine lymphocyte iron management proteins. Twenty-four women with early-onset RLS and 25 control women without RLS symptoms were studied. RESULTS: RLS and control subjects were matched for age, hemoglobin, and serum iron profile. However, transferrin receptor (TfR) and DMT1 (divalent metal transporter 1 protein) levels in lymphocytes were significantly higher for RLS patients than for controls. No significant differences in ferritin subtypes or transferrin levels were found. No significant correlations were found between lymphocyte and serum indices of iron status. INTERPRETATION: RLS lymphocytes showed an increase in ferroportin, implying increased cellular iron excretion, in the face of increased iron need (increased TfR and DMT1). In the absence of changes in H-ferritin, the findings indicate a balance between input and output with no net iron change but probable overall increase in iron turnover. The lack of any significant correlation between serum and lymphocyte iron indices indicates that iron management proteins from lymphocytes are at a minimum an alternative and independent marker of cellular iron metabolism.     

Peculiar lifespan changes of periodic leg movements during sleep in restless legs syndrome

The objective of this observational cohort study was to analyse the age‐related changes of periodic leg movements during sleep using the newest international scoring rules, to expand past analyses, including patients in the paediatric age range, and also to analyse the changes of short‐interval and isolated leg movements during sleep throughout the lifespan. One hundred and sixty‐five patients (84 women) with restless legs syndrome were recruited in the following age groups: 16 preschoolers (≤5 years of age), 29 school‐age children (6–12 years), 19 adolescents (13–17 years), 17 young adults (19–40 years), 47 adults (41–60 years) and 37 seniors (>60 years). Total, periodic, short‐interval and isolated leg movements during sleep and periodicity indexes were obtained by polysomnography. The total index showed (quartic polynomial interpolation) a decrease before 10 years, followed by a steady increase up to 30 years, a relatively stable period until 60 years, and a final increase up to 80 years. This course was almost entirely due to changes in periodic movements. Isolated movements did not change significantly and short‐interval movements showed only an increase in seniors. Our study indicates that, in restless legs syndrome, the total index shows a peculiar and unique course throughout the lifespan, mainly due to periodic movements. These age‐related changes may mirror developmental changes in network complexity known to occur in dopaminergic circuits. These data further confirm the need to better assess the periodicity of leg movements in sleep during the human development period, in order to obtain clinically useful information.     

可溶性转铁蛋白受体与血清铁蛋白在慢性炎症性疾病合并缺铁性贫血诊断中的价值比较

目的：探讨可溶性转铁蛋白受体（Soluble tranferrin receptor,sTfR）与血清铁蛋白（Serum ferritin,SFer）在慢性炎症性疾病合并缺铁性贫血（Iron deficiency anemia,IDA）诊断中的价值。方法：随机选取我院2009年8月至2011年6月收治的29例患有慢性炎症性疾病伴IDA患者,31例慢性炎症性疾病无贫血患者,以及28例健康人,进行SFer,sTfR检测。结果：sTfR在慢性炎症性疾病合并IDA组明显升高,与慢性炎症性疾病无贫血组比较有显著性差异（P〈0.01）;SFer在慢性炎症性疾病合并IDA组有降低,与慢性炎症性疾病无贫血组比较无显著性差异（P〉0.05）。结论：血清sTfR的测定较SFer更能准确反映体内铁贮存情况,对慢性炎症性疾病合并IDA的诊断具有指导意义。     

Actigraphic assessment of periodic leg movements in patients with restless legs syndrome

The diagnosis of restless legs syndrome (RLS) relies upon diagnostic criteria which are based on history only, and dopaminergic treatment is not normally the first choice of treatment for all patients. It would be worthwhile to identify patients non‐responsive to dopaminergic treatment beforehand, because they may suffer from a restless legs‐like syndrome and may require alternative treatment. We included retrospectively 24 adult patients fulfilling the four essential criteria for restless legs and 12 age‐matched healthy controls. They were investigated by ambulatory actigraphy from both legs over three nights, and patients started treatment with dopamine agonists after this diagnostic work‐up. We examined 12 responders to dopaminergic treatment and 12 non‐responders and studied the association between response to dopaminergic treatment and the periodic limb movement index (PLMI) as assessed with actigraphy. Demographic characteristics, excessive daytime sleepiness and fatigue at baseline were similar in all three groups. Baseline RLS severity was similar between responders and non‐responders [International Restless Legs Severity Scale (IRLS): 25 ± 9 and 24 ± 8]. Group comparisons of PLMI before treatment initiation showed significant differences between the three groups. Post‐hoc pairwise comparisons revealed that healthy controls had significantly lower PLMI (4.9 ± 4.5) than responders (29.3 ± 22.7) and non‐responders (13.3 ± 11.2). Similarly, the PLMI in responders was lower than in non‐responders. PLMI day‐to‐day variability did not differ between responders and non‐responders and there was no correlation between treatment effect, as assessed by the decrease of the IRLS and baseline PLMI. Our retrospective study indicates that actigraphy to assess periodic limb movements may contribute to a better diagnosis of dopamine‐responsive restless legs syndrome.     

Initial screening transferrin saturation values, serum ferritin concentrations, and HFE genotypes in Native Americans and whites in the Hemochromatosis and Iron Overload Screening Study

We compared initial screening transferrin saturation (TfSat) and serum ferritin (SF) phenotypes and HFE C282Y and H63D genotypes of 645 Native American and 43,453 white Hemochromatosis and Iron Overload Screening Study participants who did not report a previous diagnosis of hemochromatosis or iron overload. Elevated measurements were defined as TfSat >50% in men and >45% in women and SF >300 ng/ml in men and >200 ng/ml in women. Mean TfSat was 31% in Native American men and 32% in white men (p = 0.0337) and 25% in Native American women and 27% in white women (p < 0.0001). Mean SF was 153 microg/l in Native American and 151 microg/l in white men (p = 0.8256); mean SF was 55 microg/l in Native American women and 63 microg/l in white women (p = 0.0015). The C282Y allele frequency was 0.0340 in Native Americans and 0.0683 in whites (p < 0.0001). The H63D allele frequency was 0.1150 in Native Americans and 0.1532 in whites (p = 0.0001). We conclude that the screening TfSat and SF phenotypes of Native Americans are similar to those of whites. The allele frequencies of HFE C282Y and H63D are significantly lower in Native Americans than in whites.     

Gender differences in clinical,laboratory and polysomnographic features of restless legs syndrome

Restless legs syndrome is a common neurological disorder with a clear female predominance. This study aims to evaluate gender differences in clinical, laboratory and polysomnographic features in patients with restless legs syndrome. For this retrospective analysis, 42 women and 42 men from the Innsbruck RLS database matched by age and therapy were included. Demographic data as well as different severity scales (IRLS, RLS‐6 and CGI) were evaluated. Laboratory parameters included several indicators of serum iron status. In all patients, polysomnography was performed according to the AASM guidelines, and periodic leg movements during sleep were scored according to the AASM criteria. IRLS, RLS‐6 and CGI revealed more severe symptoms in women (IRLS median [range]: 17.5 [0–35] versus 13.5 [0–32], p = 0.028; RLS‐6 median [range]: 18 [0–39] versus 12 [1–42], p = 0.014). Women had lower serum ferritin levels than men (median [range] in μg L^?1: 74 [9–346] versus 167 [15–389], p < 0.001). Twenty‐two women and eight men (53.7% versus 22.2%, p = 0.003) had ferritin values below 75 μg L^?1. Periodic leg movements during sleep indices were significantly lower in women than in men (median [range] in number per hr: 11.4 [0–62.5] versus 40 [0–154], p = 0.004, and 12.6 [0–58.5] versus 40 [0.5–208], p = 0.002, for night I and night II, respectively). Restless legs syndrome severity as measured by validated scales was worse in women, while periodic leg movements during sleep indices were higher in men. These results suggest a possible gender difference in phenotypical presentation of restless legs syndrome, manifesting with predominantly sensory symptoms in women and predominantly motor symptoms in men.     

Sequence analysis of leg movements during sleep with different intervals (<10, 10–90 and >90 s) in restless legs syndrome

The aim of this study was to define the time structure of leg movements during sleep occurring with an intermovement interval (onset‐to‐onset) shorter than 10 s in patients with restless legs syndrome and controls, and to compare it to the structure of movements with intervals of 10–90 s or >90 s. Polysomnographic recordings of 141 untreated patients and 68 age‐matched normal controls were analysed. All movements were detected and classified into three categories, separated by intervals of <10, 10–90 or >90 s. The number of movements included in each category was significantly higher in patients than in controls. The movements with an interval of >90 s occurred steadily during the night, whereas the hourly distribution of movements with intervals of <10 or 10–90 s was decreasing or bell‐shaped in patients or controls, respectively. Movements with an interval of <10 s tended to have a shorter duration and constituted shorter sequences than movements with intervals of 10–90 or >90 s. The time structure features of the three categories of movements considered in this study were found to be clearly different. This, together with previous observations on the differential effects of dopamine agonists on movements with different intervals, suggests that movements with intervals of <10 and >90 s are regulated by neurotransmitter mechanisms different from those modulating movements with an interval of 10–90 s.     

Attention-deficit/hyperactivity disorder, Tourette's syndrome, and restless legs syndrome: the iron hypothesis

Preliminary but increasing evidence suggests that attention-deficit/hyperactivity disorder (ADHD), Tourette's syndrome (TS), and restless legs syndrome (RLS) may be comorbid. In the present article, we hypothesize that ADHD, TS, and RLS may be part of a spectrum, and that iron deficiency contributes to the pathophysiology underlying this spectrum. Iron deficiency might lead to ADHD, RLS and TS symptoms via its impact on the metabolism of dopamine and other catecholamines, which have been involved into the pathophysiology of ADHD, TS, and RLS. We speculate that the catecholaminergic systems are differently impacted in each of the three disorders, contributing to a different specific phenotypic expression of iron deficiency. MRI studies assessing brain iron levels in ADHD, TS, and childhood RLS, as well as genetic studies on the specific molecular pathways involved in iron deficiency, are greatly needed to confirm the iron hypothesis underlying ADHD, TS, and RLS. This body of research may set the basis for controlled trials assessing the effectiveness and tolerability, as well as the most appropriate dose, duration and type (oral vs. intravenous) of iron supplementation. In conclusion, the iron hypothesis may help us progress in the understanding of pathophysiological links between ADHD, RLS, and TS, suggesting that iron supplementation might be effective for all these three impairing conditions.     

Association of proton pump inhibitor and histamine H2-receptor antagonists with restless legs syndrome

Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H₂-receptor antagonists (H₂A) are among the most commonly used drugs worldwide and show evidence of causing iron deficiency. We conducted a case/non-case observational study of blood donors in the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS), both of which had complete blood count measures and a completed RLS assessment via the Cambridge–Hopkins RLS questionnaire. After adjusting for age, sex, race, BMI, blood donation frequency, smoking, hormone use, and iron supplement use, PPI/H₂A use was associated with RLS (odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.13–1.76; p = 0.002) in REDS-III for both PPI (OR = 1.43; CI, 1.03–1.95; p = 0.03) and H₂A (OR = 1.56; CI, 1.10–2.16; p = 0.01). DBDS exhibited a similar association with PPIs/H₂As (OR = 1.29; CI, 1.20–1.40; p < 0.001), and for PPIs alone (OR = 1.27; CI, 1.17–1.38; p < 0.001), but not H₂As alone (OR = 1.18; CI, 0.92–1.53; p = 0.2). We found no evidence of blood iron stores mediating this association. The association of PPI, and possibly H₂A, consumption with RLS independent of blood iron status and other factors which contribute to RLS risk suggest the need to re-evaluate use of PPI/H₂A in populations at particular risk for RLS.     

CSF and urine biogenic amine metabolites in Rett syndrome

The metabolites of dopamine (homovanillic acid-HVA), noradrenaline (4-hydroxy-3-methoxy-phenylglycol-HMPG), and serotonin (5-hydroxyindoleacetic acid-5-HIAA) were measured in cerebrospinal fluid (CSF) from 38 patients and urine from 36 patients with typical Rett syndrome (RS) and compared with controls of similar age. CSF metabolite concentrations were the same in the patients and controls. Urinary metabolites expressed per mol creatinine were significantly higher in older RS patients. This difference is partly explained by lower urinary creatinine levels in older RS patients, due to their known reduction in muscle mass. Alterations in CSF or urine biogenic amine metabolite concentrations do not appear to represent the primary abnormality in RS, and their measurement cannot be regarded as a reliable means of diagnosis.     

Diurnal variation of serum iron,iron-binding capacity,transferrin saturation,and ferritin levels

Serum iron levels vary throughout the day. Morning levels are generally assumed to be higher than afternoon or evening levels. We studied whether our practice of restricting serum iron collections to the morning was necessary. Serum iron, iron-binding capacity, transferrin saturation, and ferritin levels were determined on blood specimens obtained from 20 healthy adult volunteers at 8 AM, noon, and 4 PM (day 1) and 8 AM (day 2). Although statistically significant differences among mean values for the collection times were observed for iron, iron-binding capacity, and (log) ferritin, no consistent diurnal variation was seen. Morning iron levels were higher than afternoon levels for only half of the subjects. Between-day variation for all 4 analytes was similar to within-day variation. We conclude that the practice of restricting iron specimen collections to a specific time of day does not improve the reliability of the test result.     

超顺磁氧化铁标记对干细胞转铁蛋白受体和铁蛋白轻链基因及蛋白表达的影响

目的研究超顺磁氧化铁（SPIO）标记对大鼠脂肪干细胞（ADSCs）转铁蛋白受体（TfR）和铁蛋白轻链（Fn-L）基因及蛋白表达的影响。方法实验通过医院伦理委员会的批准。标记组（实验组）采用多聚赖氨酸（PLL,终质量浓度为1.5μg/mL）介导SPIO（终质量浓度为50μg/mL）标记ADSCs。在2、4、8、16、24、96、168、336、504、672 h,分别用实时荧光定量聚合酶链反应（RT-PCR）和WesternBlot实验定量检测实验组和未标记组（对照组）TfR和Fn-L基因及蛋白表达水平。结果 PLL-SPIO标记ADSCs后,实验组Fn-L mRNA（2、4、8、16、24、96、168、336 h）及蛋白（16、72、96、168 h）（P均〈0.05）表达水平会暂时性升高,至标记后一定时间,Fn-L mRNA（504、672h）及蛋白（336、504、672h）表达水平两组间差异无统计学意义（P均〉0.05）;实验组TfR mRNA（2、4、8、16、72、96、168、336 h）及蛋白（24、96 h）（P均〈0.05）表达水平会暂时性减低,至标记后一定时间,TfRmRNA（504、672 h）及蛋白（168、336、504、672 h）表达水平两组间差异无统计学意义（P均〉0.05）。结论在一定浓度内,PLL-SPIO标记ADSCs,对Fn-L和TfR基因及蛋白表达仅产生暂时性影响;从而为细胞内标记过程的安全性提供了实验依据。     

Periodic leg movements during sleep in narcoleptic patients with or without restless legs syndrome

We compared periodic and non‐periodic leg movements during sleep and polysomnography in patients with narcolepsy with cataplexy (NC) with or without restless legs syndrome (RLS) with matched idiopathic RLS (iRLS) and control subjects. We enrolled 100 patients with NC: 17 having RLS were compared with 34 sex‐ and age‐matched patients without RLS and with 17 normal controls and 17 iRLS subjects. Periodic leg movements were highest in iRLS and lowest in controls, with those in NC with RLS very close to iRLS, but higher than those in NC without RLS. The periodicity indexes showed the highest value in iRLS followed by NC with or without RLS and, finally, by controls. The inter‐leg movement intervals peaked between 10 and 50 s in NC with RLS and in iRLS, the former did not display the nocturnal gradual decrease of periodic leg movements typical of iRLS. Periodic leg movements during sleep and polysomnography displayed specific features in RLS and NC, respectively, with NC with RLS showing an intermediate pattern. Even if RLS is only detected by targeted interview in NC, its frequency and impact on night‐time sleep architecture and continuity suggest that this condition should be routinely searched for in NC.     

可溶性血清转铁蛋白受体和血清铁在诊断妊娠妇女缺铁性贫血中的比较

目的比较可溶性血清转铁蛋白受体(soluble transferrin receptor,sTfR)和血清铁(serum iron,SI)两种检测指标,在诊断妊娠妇女缺铁性贫血中的灵敏度和特异性.方法采用免疫分析法和比色法测定30例贫血妊娠妇女和30例贫血妊娠妇女和30例健康妊娠妇女的sTfR水平的SI水平,并对实验数据进行分析和比较.结果30例贫血妊娠妇女的sTfR平均值是31.3860±6.7990nmol/L,高于临界值28.1mmol/L(P＜0.05),属于贫血范围;SI的平均值是9.53±4.2622nmol/L,与临界值9nmol/L没有差异,属于正常范围.30例正常妊娠妇女的sTfR平均值是25.2080±6.9032nmol/L,小于临界值28.1nmol/L(P＜0.05),属于正常范围;SI的平均值是13.3733±4.8359nmol/L,高于临界值属于正常范围(P＜0.01).贫血妊娠妇女的sTfR水平明显高于正常妊娠妇女的sTfR水平(P＜0.01)、SI水平明显低于正常妊娠妇女(P＜0.01).sTfR、SI测定妊娠妇女缺铁性贫血的灵敏度分别是70%和53.3%、特异性分别是83.3%和80.0%.结论在诊断妊娠妇女缺铁性贫血,两种指标的特异性都比较高,但sTfR测定比SI测定灵敏性高、能更正确地对妊娠妇女是否缺铁做出正确判断.     

Expression of transferrin receptor and ferritin following ferumoxides-protamine sulfate labeling of cells: implications for cellular magnetic resonance imaging

Ferumoxides-protamine sulfate (FE-Pro) complexes are used for intracellular magnetic labeling of cells to non-invasively monitor cell trafficking by in vivo MRI. FE-Pro labeling is non-toxic to cells; however, the effects of FE-Pro labeling on cellular expression of transferrin receptor (TfR-1) and ferritin, proteins involved in iron transport and storage, has not been reported. FE-Pro-labeled human mesenchymal stem cells (MSCs), HeLa cells and primary macrophages were cultured from 1 week to 2 months and evaluated for TfR-1 and ferritin gene expression by RT-PCR and protein levels were determined using Western blots. MTT (proliferation assay) and reactive oxygen species (ROS) analysis were performed. FE-Pro labeling of HeLa and MSCs resulted in a transient decrease in TfR-1 mRNA and protein levels. In contrast, Fe-Pro labeling of primary macrophages resulted in an increase in TfR-1 mRNA but not in TfR-1 protein levels. Ferritin mRNA and protein levels increased transiently in labeled HeLa and macrophages but were sustained in MSCs. No changes in MTT and ROS analysis were noted. In conclusion, FE-Pro labeling elicited physiological changes of iron metabolism or storage, validating the safety of this procedure for cellular tracking by MRI.     

Ferritin levels in the cerebrospinal fluid and restless legs syndrome: effects of different clinical phenotypes

STUDY OBJECTIVE: To determine whether patients with restless legs syndrome (RLS) and controls differ in regard to levels of ferritin and transferrin in the cerebrospinal fluid (CSF) when samples are collected at night, to determine whether patients with early-onset and late-onset RLS show a different outcome for CSF values, and to determine whether the CSF ferritin level correlates with disease severity. DESIGN: Collection of CSF and plasma; assessment of disease severity using objective (periodic limb movements) and subjective (Johns Hopkins Restless Legs Severity Scale) measures of severity. SETTING: General Clinical Research Center. PARTICIPANTS: Thirty subjects with idiopathic RLS (15 early- and 15 late-onset RLS) and 22 age- and sex-matched controls. INTERVENTION: N/A. RESULTS: Nighttime CSF ferritin levels were lower in the total RLS group compared with controls. Further assessment found that the early-onset (less than 45 years of age) but not the late-onset (greater than or equal to 45 years of age) RLS group had significantly lower CSF ferritin levels compared with controls. There was a strong correlation between the age of symptom onset and CSF ferritin values (r = 0.64): the earlier the age, the lower the ferritin level. A regression analysis showed that both sex and RLS subtype had significant effects on the CSF ferritin level, with women with early-onset RLS having substantial lower values than men with late-onset RLS. A comparison between these nighttime CSF values and previously published daytime samples suggests that diurnal changes may have effects on the findings. CONCLUSIONS: This study is distinct in showing that the degree of the CSF-ferritin effect is best defined by the clinical phenotypes of sex and age of symptom onset and by the time of day that samples are collected.     

Protein tyrosine phosphatase receptor type delta (PTPRD) gene in an animal model of restless legs syndrome

The pathophysiology of the restless legs syndrome (RLS) is related to dopaminergic dysfunction, reduced iron and variations in gene expression, such as the protein tyrosine phosphatase receptor type delta gene (PTPRD). Animal models could be key to achieving a mechanistic understanding of RLS and to facilitate efficient platforms for evaluating new therapeutics. Thus, the aim of this study was to evaluate the expression of PTPRD, of genes and proteins associated with RLS, the sleep patterns and the cardiovascular parameters in an animal model of RLS (spontaneously hypertensive rat [SHR]). Rats were divided into two groups: (i) Wistar-Kyoto and (ii) SHR. Cardiovascular parameters were assessed by tail plethysmography. Polysomnography was used to analyse the sleep pattern (24 h). For the PTPRD analyses, quantitative polymerase chain reaction (qPCR) and indirect enzyme-linked immunosorbent assay (ELISA) techniques were used. To evaluate the tyrosine hydroxylase enzyme, dopamine transporter (DAT) and type 2 dopaminergic receptor, qPCR and Western Blotting techniques were used. For the quantification of iron, ferritin and transferrin, the ELISA method was used. SHRs had higher blood pressure, alterations in sleep pattern, lower expression of protein content of PTPRD, lower expression of DAT, and lower serum concentrations of ferritin. These data suggest that the behavioural, physiological, and molecular changes observed in SHRs provide a useful animal model of RLS, reinforcing the importance of this strain as an animal model of this sleep disorder.     

TNF polymorphisms in Alzheimer disease and functional implications on CSF beta-amyloid levels

Alzheimer disease (AD), vascular dementia, and stroke are all associated with inflammation though their respective initiating factors differ. Recently a polymorphism in the proinflammatory cytokine tumor necrosis factor (TNF), in association with apolipoprotein E (APOE), was reported to increase AD risk. Two SNPs, rs1799724 (-850C>T; NT_007592.14:g.22400733C>T) and rs1800629 (-308G>A; [NT_007592.14:g.22401282G>A]), and the APOE polymorphism were genotyped in 506 patients with sporadic AD and in 277 cognitively healthy controls. In a subset of 90 individuals we also investigated whether these SNPs exerted any functional effects on cerebrospinal fluid (CSF) beta-amyloid (Abeta) levels. The frequency of the rs1799724 genotypes and the rs1799724-T allele were significantly different in AD individuals (P=0.009; odds ratio [OR], 1.63; 95% confidence interval [CI], 1.13-2.34), while the rs1800629 SNP was not associated with AD. Significant interaction was observed between the rs1799724-T and APOE epsilon4 alleles in that the rs1799724-T allele significantly modified risk associated with possession of the epsilon4 allele only (epsilon4 in absence of rs1799724-T: OR, 2.92; 95% CI, 2.00-4.27; epsilon4 in presence of rs1799724-T: OR, 6.65; 95% CI, 3.26-13.55; P=0.03). Haplotyping analysis revealed a significant overrepresentation of an rs1799724-T/rs1800629-G haplotype in AD (P=0.012; OR, 1.60; 95% CI, 1.11-2.29), although to a lesser degree than rs1799724-T alone. Further, the rs1799724-T allele was found to be associated with lower levels of CSF Abeta42 (P=0.023), thus corroborating the genetic findings. Inheritance of the rs1799724-T allele appears to synergistically increase the risk of AD in APOEepsilon4 carriers and is associated with altered CSF Abeta42 levels. Further investigations are warranted to assess the significance of these novel findings.     

Association between irritable bowel syndrome and restless legs syndrome in the general population

This study aimed to explore the association between restless legs syndrome and irritable bowel syndrome in an epidemiological cohort. We included 3365 adults, of whom 1602 were female (age 52.5 ± 7.5 years), who had participated in the Korean Genome and Epidemiology Study (2005–2006). The diagnosis of restless legs syndrome was based on the criteria proposed by the International Restless Legs Syndrome Study Group, and irritable bowel syndrome was defined according to the Rome II criteria. The prevalence of each condition was determined and their association was tested by logistic regression analysis. Age, sex, haemoglobin concentration, renal insufficiency, use of medications and depressive mood were all adjusted for. The prevalence of restless legs syndrome and irritable bowel syndrome was 4.5 and 11.1%, respectively. Irritable bowel syndrome was more prevalent in the group with restless legs syndrome (24.0 versus 10.5%, P < 0.001). Subjects with restless legs syndrome were older (54.2 ± 8.4 versus 52.4 ± 7.4, P = 0.006) and more depressive (26.7 versus 12.5%, P < 0.001), and were predominantly female (57.3 versus 47.2%, P = 0.015), had more frequent insomnia symptoms (44.0 versus 28.2%, P < 0.001), had lower haemoglobin concentration (13.7 ± 1.5 versus 14.1 ± 1.6 g dL^?1P = 0.004) and higher highly sensitive C‐reactive protein (1.8 ± 5.1 versus 1.4 ± 2.9 mg dL^?1, P = 0.08). The adjusted odds ratio of restless legs syndrome in relation to irritable bowel syndrome was 2.59 (1.74–3.85, P < 0.001). Irritable bowel syndrome appeared to be associated with restless legs syndrome independently from other major risk factors for restless legs syndrome. Searching for the mechanisms underlying this association is indicated.