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
Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
Mov Disord. 2014 Dec;29(14):1825-8. doi: 10.1002/mds.26044. Epub 2014 Sep 25.
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 NALCN gene region.
We performed a case-control association study in a Spanish population. The SNPs selected for genotyping were two SNPS in the NALCN gene (rs61973742 and rs1338041), one SNP in the OR4X2 gene (rs67863238), one SNP in the COL4A1 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.
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.
We did not find any evidence supporting the association of NALCN with cervical dystonia, indicating that this gene is not implicated in the pathogenesis of this disorder in our cervical dystonia population.
最近一项全基因组关联研究（GWAS）在英国人群的几个区域中发现了与颈部肌张力障碍存在推测性关联，但未经统计学证实。因此，作者提出离子通道NALCN（非选择性钠漏通道）功能障碍可能是颈部肌张力障碍的一个合理病因。我们研究的目的是调查先前在一项英国GWAS中报道的五个单核苷酸多态性（SNP）作为颈部肌张力障碍潜在遗传风险因素的关联，其中包括位于NALCN基因区域的两个SNP。
我们在西班牙人群中进行了一项病例对照关联研究。选择进行基因分型的SNP是NALCN基因中的两个SNP（rs61973742和rs1338041）、OR4X2基因中的一个SNP（rs67863238）、COL4A1区域中的一个SNP（rs619152）以及一个基因间SNP（rs1249277）。从252例颈部肌张力障碍患者中收集基因组DNA，这些患者的平均年龄为55.3±14.1岁（平均发病年龄为43.5±15.7岁），以及342名无关对照受试者，平均年龄为56.3±14.3岁。使用TaqMan分析和SimpleProbe分析对SNP进行基因分型。
由于分析失败，SNP rs619152必须排除。对于所有分析的SNP，病例组和对照组之间的等位基因分布没有发现显著差异。因此，在我们的西班牙人群中，我们没有发现分析的SNP与颈部肌张力障碍有关联。
我们没有发现任何证据支持NALCN与颈部肌张力障碍的关联，这表明在我们的颈部肌张力障碍人群中，该基因与这种疾病的发病机制无关。
