Lack of Validation of Variants Associated With Cervical Dystonia Risk: A GWAS Replication Study

被引：16

作者：

Gomez-Garre, Pilar ^{[1
]}

Huertas-Fernandez, Ismael ^{[1
]}

Teresa Caceres-Redondo, Maria ^{[1
]}

Alonso-Canovas, Araceli ^{[2
]}

Bernal-Bernal, Inmaculada ^{[1
]}

Blanco-Ollero, Alberto ^{[3
]}

Bonilla-Toribio, Marta ^{[1
]}

Andres Burguera, Juan ^{[4
]}

Carballo, Manuel ^{[1
]}

Carrillo, Fatima ^{[1
]}

Jose Catalan-Alonso, M. ^{[5
]}

Escamilla-Sevilla, Francisco ^{[6
]}

Espinosa-Rosso, Raul ^{[7
]}

Carmen Fernandez-Moreno, Maria ^{[8
]}

Garcia-Caldentey, Juan ^{[9
]}

Manuel Garcia-Moreno, Jose ^{[10
]}

Giacometti-Silveira, Sandra ^{[11
]}

Gutierrez-Garcia, Javier ^{[12
]}

Jesus-Maestre, Silvia ^{[1
,13
]}

Lopez-Valdes, Eva ^{[5
]}

Carlos Martinez-Castrillo, Juan ^{[2
]}

Pilar Medialdea-Natera, Maria ^{[14
]}

Mendez-Lucena, Carolina ^{[10
]}

Minguez-Castellanos, Adolfo ^{[6
]}

Angel Moya, Miguel ^{[7
]}

Jose Ochoa-Sepulveda, Juan ^{[15
]}

Ojea, Tomas ^{[11
]}

Rodriguez, Nuria ^{[16
]}

Rubio-Agusti, Ignacio ^{[4
]}

Sillero-Sanchez, Miriam ^{[16
]}

del Val, Javier ^{[9
]}

Vargas-Gonzalez, Laura ^{[1
]}

Mir, Pablo ^{[1
]}

机构：

[1] Univ Seville, Unidad Trastornos Movimiento, Serv Neurol & Neurofisiol Clin, Hosp Univ Virgen del Rocio,CSIC, Seville, Spain

[2] Hosp Ramon & Cajal, IRYCIS, Unidad Trastornos Movimiento, Serv Neurol, E-28034 Madrid, Spain

[3] Hosp Juan Ramon Jimenez, Serv Neurol, Huelva, Spain

[4] Hosp La Fe, Serv Neurol, Unidad Trastornos Movimiento, E-46009 Valencia, Spain

[5] Hosp Clin San Carlos, Serv Neurol, Unidad Trastornos Movimiento, Madrid, Spain

[6] Hosp Univ Virgen de las Nieves, Unidad Trastornos Movimiento, Serv Neurol, Granada, Spain

[7] Hosp Univ Puerta del Mar, Serv Neurol, Cadiz, Spain

[8] Hosp Virgen de Valme, Serv Neurol, Seville, Spain

[9] Fdn Jimenez Diaz, Serv Neurol, Unidad Trastornos Movimento, Madrid, Spain

[10] Hosp Univ Virgen Macarena, Serv Neurol, Seville, Spain

[11] Hosp Carlos Haya, Serv Neurol, Malaga, Spain

[12] Hosp Univ San Cecilio, Serv Neurol, Granada, Spain

[13] Ctr Hosp Jaen, Serv Neurol, Jaen, Spain

[14] Hosp Univ Virgen de la Victoria, Serv Neurol, Unidad Trastornos Movimiento, Malaga, Spain

[15] Hosp Univ Reina Sofia, Serv Neurol, Cordoba, Spain

[16] Hosp Univ Puerto Real, Serv Neurol, Cadiz, Spain

来源：

MOVEMENT DISORDERS | 2014年 / 29卷 / 14期

关键词：

primary dystonia; cervical dystonia; replication; association study; GWAS; MUTATIONS; CHANNEL;

D O I：

10.1002/mds.26044

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: 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. Methods: 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 55.3614.1 years (mean age at onset, 43.5615.7 years), and 342 unrelated control subjects with a mean age of 56.3614.3 years. Genotyping of SNPs was performed using Taq-Man assays and SimpleProbe assays. Results: 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. Conclusions: 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. (C) 2014 International Parkinson and Movement Disorder Society

引用

页码：1825 / 1828

页数：5

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