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Evidence for a genetic association between monoamine oxidase A and restless legs syndrome
A Desautels1, G Turecki, J Montplaisir
1Centre d'étude du sommeil, Hôpital du Sacré-Coeur de Montréal and Centre de recherche en sciences neurologiques, Université de Montréal, Quebec, Canada.
Background:
Impairment in the central dopaminergic system has been consistently suggested as an etiologic factor in restless legs syndrome (RLS).
Objective:
To investigate a possible role for the MAOA and MAOB genes in RLS using a population-based association study.
Methods:
In addition to a dinucleotide repeat located within the second intron of the MAOB gene, a functional variable number of tandem repeat (VNTR) polymorphism recently identified in the MAOA gene promoter region was examined, using 96 extensively characterized patients and 200 control subjects matched for ethnic background. The relationship between variation at these loci and several clinical features was also considered.
Results:
Pertaining to the MAOA gene, females with the high activity allele had a greater risk (OR: 2.0; 95% CI: 1.06 to 3.77) of being affected with RLS than females carrying the low activity alleles. The authors did not observe this association among the male subjects (OR: 0.98; 95% CI: 0.31 to 3.14). Interestingly, females carrying the high transcription alleles showed a longer sleep onset latency (U = 163.5; p = 0.015) and exhibited a higher movement index during the Suggested Immobilization Test (Student's t-test = -2.02; p = 0.048). No differences were observed regarding the MAOB gene in our sample.
Conclusions:
The high activity allele of the MAOA gene may represent a modifying factor involved in the severity of RLS manifestations in females.