Serum vitamin D, vitamin D receptor and binding protein genes polymorphisms in restless legs syndrome.

Background/objectives: Several studies showed lower serum 25-hydroxyvitamin D levels in patients with idiopathic restless legs syndrome (RLS) compared with matched controls, and a single study showed an association between the rs731236 single nucleotide polymorphism (SNP) in the vitamin D receptor (VDR) gene and the risk for RLS. We aimed to study the relationship between the serum 25-hydroxyvitamin D levels and to confirm previous findings related to SNPs in the VDR and the GC vitamin D binding protein (GC) gene, with the risk for RLS in the Spanish Caucasian population.

Methods: We genotyped 285 idiopathic RLS patients and 325 age and sex-matched controls for VDRrs2228750, VDRrs7975232, VDRrs739837, VDRrs78783628, GCrs7041 and GCrs4588 SNPs using TaqMan assays, and determined serum 25-hydroxyvitamin D levels in 111 idiopathic RLS patients and 167 controls using an ELISA commercial kit.

Results: Serum 25-hydroxyvitamin D levels were significantly higher in RLS patients than in controls but were unrelated with the 7 SNPs studied. None of the 7 SNPs analyzed was associated with the risk for idiopathic RLS or with a positive family history of RLS. However, RLS patients carrying the rs7975232CC genotype or the rs7975232C allele, had a higher frequency of response to GABAergic drugs. Associations between the age at onset and the severity of RLS with SNPs were inconsistent.

Conclusions: This study shows an association between increased serum concentrations of 25-hydroxyvitamin D and a lack of association between 7 SNPs in the VDR and in the GC genes with RLS in the Spanish Caucasian population.