Genetic association studies of neurotensin gene and restless legs syndrome in French Canadians.
OBJECTIVE
The neurotensin gene (NTS), a known dopamine modulator, is located within the candidate region for the first genetic locus of restless legs syndrome (RLS1) on chromosome 12q. Though no causative mutation was found in selected patients in a previous mutation analysis, the involvement of NTS in RLS cannot be completely excluded as a potential positional and functional candidate gene. The purpose of the current study is to further explore the NTS gene for potential functional variant(s) in its entire genomic and potential regulatory regions and their possible association with RLS symptoms.


METHODS
We resequenced the coding regions and sequenced all the intronic and potential regulatory regions of the NTS gene in additional patients and controls. We carried out full scale gene-based case-control and family-based genetic association studies using the sequence variants detected during mutational analysis.


RESULTS
No coding or variants in regulatory and intronic regions compatible with a deleterious mutation were detected. Seven polymorphisms with elevated allele frequencies in the Caucasian population did not show association with RLS in two independent case-control groups and 110 RLS families.


CONCLUSIONS
The NTS gene on chromosome 12q is most unlikely to play a direct role in RLS etiology.
Xiong
Lan
L
Center for the Study of Brain Diseases, CHUM Research Center - Notre Dame Hospital, University of Montreal, Bureau Y-3616-2, 1560, rue Sherbrooke Est, Montréal, Que., Canada H2L 4MI.
Levchenko
Anastasia
A
Montplaisir
Jacques
J
Rivière
Jean-Baptiste
JB
Thibodeau
Pascale
P
St-Onge
Judith
J
Gaspar
Claudia
C
Desautels
Alex
A
Lespérance
Paul
P
Chouinard
Sylvain
S
Turecki
Gustavo
G
Rouleau
Guy A
GA
D000328:Adult; D000368:Aged; D000483:Alleles; D002170:Canada; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009496:Neurotensin / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012148:Restless Legs Syndrome / Q000235:genetics*; D017421:Sequence Analysis; D012737:Sex Factors; D005879:Tourette Syndrome / Q000235:genetics; D020506:Untranslated Regions / Q000235:genetics
D020506:Untranslated Regions; D009496:Neurotensin