Lack of validation of variants associated with cervical dystonia risk: A GWAS replication study. Issue 14 (25th September 2014)

• Record Type: Journal Article
• Authors: Gómez‐Garre, Pilar; Huertas‐Fernández, Ismael; Cáceres‐Redondo, María Teresa; Alonso‐Canovas, Araceli; Bernal‐Bernal, Inmaculada; Blanco‐Ollero, Alberto; Bonilla‐Toribio, Marta; Burguera, Juan Andrés; Carballo, Manuel; Carrillo, Fatima; José Catalán‐Alonso, M.; Escamilla‐Sevilla, Francisco; Espinosa‐Rosso, Raul; Carmen Fernández‐Moreno, María; García‐Caldentey, Juan; García‐Moreno, José Manuel; Giacometti‐Silveira, Sandra; Gutiérrez‐García, Javier; Jesús‐Maestre, Silvia; López‐Valdés, Eva; Martínez‐Castrillo, Juan Carlos; Medialdea‐Natera, María Pilar; Méndez‐Lucena, Carolina; Mínguez‐Castellanos, Adolfo; Angel Moya, Miguel; Ochoa‐Sepulveda, Juan José; Ojea, Tomas; Rodríguez, Nuria; Rubio‐Agusti, Ignacio; Sillero‐Sánchez, Miriam; del Val, Javier; Vargas‐González, Laura; Mir, Pablo;
• Is Part Of: Movement disorders. Volume 29:Issue 14(2014)
• Page Start: 1825
• Page End: 1828
• Publication Date: 2014-09-25
• Subjects: Movement disorders -- Periodicals; 610
• DOI: 10.1002/mds.26044
• Languages: English
• ISSNs: 0885-3185

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="mds26044-sec-0001" sec-type="section"> <title>Background</title> <p>A recent genome‐wide association study (GWAS) has identified a putative association, not statistically confirmed, of cervical dystonia within several regions in a British population. Hence, the authors proposed dysfunction of the ion channel NALCN (for sodium leak channel, nonselective) as a plausible cause of cervical dystonia. The objective of our study was to investigate the association of five single nucleotide polymorphisms (SNPs) previously reported with high signals as putative genetic risk factors for cervical dystonia in a British GWAS, including two located in the <italic>NALCN</italic> gene region.</p> </sec> <sec id="mds26044-sec-0002" sec-type="section"> <title>Methods</title> <p>We performed a case‐control association study in a Spanish population. The SNPs selected for genotyping were two SNPS in the <italic>NALCN</italic> gene (rs61973742 and rs1338041), one SNP in the <italic>OR4X2</italic> gene (rs67863238), one SNP in the <italic>COL4A1</italic> region (rs619152), and one intergenic SNP (rs1249277). Genomic DNA was collected from 252 patients with cervical dystonia, with a mean age of 55.3 ± 14.1 years (mean age at onset, 43.5 ± 15.7 years), and 342 unrelated control subjects with a mean age of 56.3 ± 14.3 years. Genotyping of SNPs was performed using TaqMan assays and SimpleProbe assays.</p> </sec> <sec id="mds26044-sec-0003" sec-type="section"> <title>Results</title> <p>The SNP rs619152 had to be excluded because of assay failure. No significant differences were found in allele distribution between cases and controls for all analyzed SNPs. Therefore, we found no association with cervical dystonia for the analyzed SNPs in our Spanish population.</p> </sec> <sec id="mds26044-sec-0004" sec-type="section"> <title>Conclusions</title> <p>We did not find any evidence supporting the association of <italic>NALCN</italic> with cervical dystonia, indicating that this gene is not implicated in the pathogenesis of this disorder in our cervical dystonia population. © 2014 International Parkinson and Movement Disorder Society</p> </sec> </abstract>