Neuronal nitric oxide synthase (nNOS, NOS1) rs693534 and rs7977109 variants and risk for restless legs syndrome
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Several biochemical, neuropathological, and experimental data suggest a possible role of nitric oxide (NO) in the pathophysiology of restless legs syndrome (RLS). Two single nucleotide polymorphisms (SNPs) neuronal nitric oxide synthase (nNOS or NOS1) gene (rs7977109 and rs693534) have been found to be associated with the risk for RLS in Germans, although only one of them (rs7977109) remained as significant after multiple comparison tests. The aim of our study was to replicate the possible association between these SNPs and risk for RLS in the Spanish population. We studied the allelic and genotype frequencies of the SNPs rs7977109 and rs693534 in 205 patients with RLS and 328 healthy controls using TaqMan genotyping. The rs7977109 and rs693534 genotypes and allelic frequencies did not significantly differ between patients with RLS and controls and were unrelated with the age at onset of RLS, gender, ferritin levels, and response to dopaminergic or gabaergic agents. The rs7999109GA genotype was overrepresented in RLS patients with positive family history of RLS, and in patients with symptomatic response to clonazepam. The results of our study suggest that these two NOS1 SNPs are not related to the overall risk for RLS in the Spanish population.
KeywordsRestless legs syndrome Genetics NOS1 gene Polymorphisms Risk factors Nitric oxide Oxidative stress
Financed by Grants PI12/00241, PI12/00324, and RETICS RD12/0013/0002 (Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Madrid, Spain); GR10068 (Junta de Extremadura, Mérida, Spain), and PRIS10016 (Fundesalud, Mérida, Spain). Partially financed with FEDER funds.
Conflict of interest
None of the authors reported conflicts of interest.
- Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisir J (2003) Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology: a report from the restless legs syndrome diagnosis and epidemiology work shop at the National Institute of Health. Sleep Med 4:101–119CrossRefPubMedGoogle Scholar
- Allen RP, Picchietti DL, Garcia-Borreguero D, Ondo WG, Walters AS, Winkelmann JW, Zucconi M, Ferri R, Trenkwalder C, Lee HB, International Restless Legs Syndrome Study Group (2014) Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated international restless legs syndrome study group (IRLSSG) consensus criteria—history, rationale, description, and significance. Sleep Med 15:860–873CrossRefPubMedGoogle Scholar
- Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Statist Soc Ser B 1:289–300Google Scholar
- Ekbom KA (1945) Restless legs. Acta Med Suppl 158:5–123Google Scholar
- Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E, Agúndez JAG (2013a) Latest perspectives in genetic risk factors for restless legs syndrome. Eur Neurol Rev 8:90–96Google Scholar
- Jiménez-Jiménez FJ, Alonso-Navarro H, Martínez C, Zurdo M, Turpín-Fenoll L, Millán J, Adeva-Bartolomé T, Cubo E, Navacerrada F, Rojo-Sebastián A, Rubio L, Calleja M, Plaza-Nieto JF, Pilo-de-la-Fuente B, Arroyo-Solera M, Agúndez JAG, García-Martín E (2013b) Dopamine receptor D3 (DRD3) gene rs6280 variant and risk for restless legs syndrome. Sleep Med 14:382–384CrossRefPubMedGoogle Scholar
- Jiménez-Jiménez FJ, Alonso-Navarro H, Martínez C, Zurdo M, Turpín-Fenoll L, Millán-Pascual J, Adeva-Bartolomé T, Cubo E, Navacerrada F, Rojo-Sebastián A, Rubio L, Calleja M, Plaza-Nieto JF, Pilo-de-la-Fuente B, Arroyo-Solera M, García-Martín E, Agúndez JAG (2014) The solute carrier family 1 (glial high affinity glutamate transporter), member 2 gene, SLC1A2, rs3794087 variant and assessment risk for restless legs syndrome. Sleep Med 15:266–268CrossRefPubMedGoogle Scholar
- Roco A, Jiménez-Jiménez FJ, Alonso-Navarro H, Martínez C, Zurdo M, Turpín-Fenoll L, Millán J, Adeva-Bartolomé T, Cubo E, Navacerrada F, Rojo-Sebastián A, Rubio L, Calleja M, Plaza-Nieto JF, Pilo-de-la-Fuente B, Arroyo-Solera M, García-Martín E, Agúndez JA (2013) MAPT1 gene rs1052553 variant is unrelated with the risk for restless legs syndrome. J Neural Transm 120:463–467CrossRefPubMedGoogle Scholar
- Winkelmann J, Lichtner P, Schormair B, Uhr M, Hauk S, Stiasny-Kolster K, Trenkwalder C, Paulus W, Peglau I, Eisensehr I, Illig T, Wichmann HE, Pfister H, Golic J, Bettecken T, Pütz B, Holsboer F, Meitinger T, Müller-Myhsok B (2008) Variants in the neuronal nitric oxide synthase (nNOS, NOS1) gene are associated with restless legs syndrome. Mov Disord 23:350–358CrossRefPubMedGoogle Scholar