Background and purpose: 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 and subjects: 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.
Conclusion: The NTS gene on chromosome 12q is most unlikely to play a direct role in RLS etiology.