Association of low ferritin with PLM in the Wisconsin Sleep Cohort.
OBJECTIVE
The origins of periodic leg movements (PLMs), a strong correlate of restless legs syndrome (RLS), are uncertain. This study was performed to assess the relationship between PLMs and peripheral iron deficiency, as measured with ferritin levels corrected for inflammation.


METHODS
We included a cross-sectional sample of a cohort study of 801 randomly selected people (n = 1008 assays, mean age 58.6 ± 0.3 years) from Wisconsin state employee agencies. A previously validated automatic detector was used to measure PLMs during sleep. The patients were categorized into RLS symptoms-positive and RLS symptoms-negative based on a mailed survey response and prior analysis. Analyses were performed using a linear model with PLM category above and below 15 PLM/h (periodic leg movement index, PLMI) as the dependent variable, and adjusting for known covariates, including previously associated single-nucleotide polymorphisms (SNPs) within BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD. Ferritin and C-reactive protein (CRP) levels were measured in serum, and ferritin levels corrected for inflammation using CRP levels.


RESULTS
After controlling for cofactors, PLMI ≥ 15 was associated with low (≤50 ng/mL) ferritin levels (OR = 1.55, p = 0.020). The best model was found using quasi-least squares regression of ferritin as a function of PLMI, with an increase of 0.0034 PLM/h predicted by a decrease of 1 ng/mL ferritin (p = 0.00447).


CONCLUSIONS
An association was found between low ferritin and greater PLMs in a general population of older adults, independent of genetic polymorphisms, suggesting a role of low iron stores in the expression of these phenotypes. Patients with high PLMI may require to be checked for iron deficiency.
Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, CA, USA.
Jason
J
Li
Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, CA, USA.
Hyatt
H
Moore
Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, CA, USA.
Ling
L
Lin
Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI, USA.
Terry
T
Young
Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI, USA.
Laurel
L
Finn
Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI, USA.
Paul E
PE
Peppard
Department of Population Health Sciences, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: mignot@stanford.edu.
Emmanuel
E
Mignot
D018798:Anemia, Iron-Deficiency / Q000150:complications*; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005293:Ferritins / Q000097:blood / Q000172:deficiency*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D020189:Nocturnal Myoclonus Syndrome / Q000209:etiology*; D020641:Polymorphism, Single Nucleotide; D017286:Polysomnography; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics; D012890:Sleep; D011795:Surveys and Questionnaires; D014922:Wisconsin
D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D002097:C-Reactive Protein; D005293:Ferritins; C090899:PTPRD protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2
Ferritin; Iron; Periodic leg movements; Restless legs syndrome; Wisconsin Sleep Cohort