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CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2016; 74(06): 445-449
DOI: 10.1590/0004-282X20160061
ARTICLES

The rs3857059 variant of the SNCAgene is associated with Parkinson’s disease in Mexican Mestizos

A variante rs3857059 do gene SNCA é associada à doença de Parkinson em mestiços mexicanos
S. García
1   Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Centro Médico Nacional “20 de Noviembre”, México DF, México;
,
G. Chavira-Hernández
1   Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Centro Médico Nacional “20 de Noviembre”, México DF, México;
,
M.P Gallegos-Arreola
2   Centro de Investigación Biomédica de Occidente, IMSS, Jalisco, México;
,
L. Dávila-Maldonado
3   Instituto de Ciencias Médicas y de la Nutrición Salvador Zubirán, México DF, México.
,
F. García Martínez
1   Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Centro Médico Nacional “20 de Noviembre”, México DF, México;
,
L.A Montes Almanza
1   Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Centro Médico Nacional “20 de Noviembre”, México DF, México;
,
C. Palma-Flores
1   Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Centro Médico Nacional “20 de Noviembre”, México DF, México;
,
P. Mondragón-Terán
1   Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Centro Médico Nacional “20 de Noviembre”, México DF, México;
,
S.L. Alcaraz Estrada
1   Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Centro Médico Nacional “20 de Noviembre”, México DF, México;
,
L. B. López-Hernández
1   Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Centro Médico Nacional “20 de Noviembre”, México DF, México;
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ABSTRACT

Among the candidate genes for Parkinson’s disease (PD), SNCAhas replicated association in different populations. Besides other known mutations in the SNCAgene, the rs3857059 variant has also been linked to various neurodegenerative disorders. Therefore, the aim of the present study was to search for association of this variant and sporadic PD in Mexican Mestizo patients. A case-control study was performed including 241 individuals, 106 patients, and 135 healthy controls. Genotyping was performed using real-time PCR. The rs3857059 variant demonstrated an association with PD in Mexican Mestizos (OR = 2.40, CI, 1.1 to 5.1, p = 0.02) under the recessive model. In addition, a gender effect was found for the GG genotype in females (OR = 1.31, CI, 1.01 to 1.7, p = 0.037). This is the first study to confirm an association of the rs3857059 variant with PD and also to show a gender effect. Our data contribute to the elucidation of the link between rs3857059 and susceptibility to PD observed in the Mexican Mestizo population.

RESUMO

Entre genes candidatos para a doença de Parkinson (PD), SNCA foi replicado em diferentes populações. Além de outras mutações conhecidas no gene SNCA, a variante rs3857059 também tem sido associada a várias doenças neurodegenerativas. Portanto, o objetivo do presente estudo foi o de procurar variante de associação e PD esporádica em pacientes mestiços mexicanos. Um estudo de caso-controle foi executado, incluindo 241 indivíduos, 106 pacientes e 135 controles saudáveis. A genotipagem foi realizada utilizando PCR em tempo real. A variante rs3857059 se mostrou associada a PD em mexicano-mestiços (OR = 2,40, IC 1,1-5,1, p = 0,02) sob o modelo recessivo. Além disso, um efeito de gênero foi encontrado para o genótipo GG no sexo feminino (OR = 1,31, CI, 1,01-1,7, p = 0,037). Este é o primeiro estudo que confirma associação da variante rs3857059 para a PD e também um efeito de gênero. Nossos dados contribuem para elucidar suscetibilidade à PD observada na população mexicana-mestiça.

Parkinson disease - genes - SNCA - genetics
doença de Parkinson - genes SNCA - genética

Support:

Support: E015-2012 ISSSTE institutional program.




Publication History

Received: 05 February 2015

Accepted: 02 March 2016

Article published online:
06 September 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Kim HJ. Alpha-synuclein expression in patients with Parkinson’s disease: a clinician’s perspective. Exp Neurobiol. 2013;22(2):77-83. doi:10.5607/en.2013.22.2.77
  • 2 Bendor JT, Logan TP, Edwards RH. The function of α-synuclein. Neuron. 2013;79(6):1044-66. doi:10.1016/j.neuron.2013.09.004
  • 3 Scholz SW, Houlden H, Schulte C, Sharma M, Li A, Berg D et al. SNCA variants are associated with increased risk for multiple system atrophy. Ann Neurol. 2009;65(5):610-4. doi:10.1002/ana.21685
  • 4 Linnertz C, Lutz MW, Ervin JF, Allen J, Miller NR, Welsh-Bohmer KA et al. The genetic contributions of SNCA and LRRK2 genes to Lewy Body pathology in Alzheimer’s disease. Hum Mol Genet. 2014;23(18):4814-21. doi:10.1093/hmg/ddu196
  • 5 Simón-Sánchez J, Schulte C, Bras JM, Sharma M, Gibbs JR, Berg D et al. Genome-wide association study reveals genetic risk underlying Parkinson’s disease. Nat Genet. 2009;41(12):1308-12. doi:10.1038/ng.487
  • 6 Liu J, Xiao Q, Wang Y, Xu ZM, Wang Y, Yang Q et al. Analysis of genome-wide association study-linked loci in Parkinson’s disease of Mainland China. Mov Disord. 2013;28(13):1892-5. doi:10.1002/mds.25599
  • 7 Ding H, Sarokhan AK, Roderick SS, Bakshi R, Maher NE, Ashourian P et al. Association of SNCA with Parkinson: replication in the Harvard NeuroDiscovery Center Biomarker Study. Mov Disord. 2011;26(12):2283-6. doi: 10.1002/mds.23934
  • 8 Flierl A, Oliveira LM, Falomir-Lockhart LJ, Mak SK, Hesley J, Soldner F et al. Higher vulnerability and stress sensitivity of neuronal precursor cells carrying an alpha-synuclein gene triplication. PLoS One. 2014;9(11):e112413. doi:10.1371/journal.pone.0112413
  • 9 Kanaan NM, Manfredsson FP. Loss of functional alpha-synuclein: a toxic event in Parkinson’s disease? J Parkinsons Dis. 2012;2(4):249-67. doi:10.3233/JPD-012138
  • 10 Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ. The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain. 2002;125(4):861-70. doi:10.1093/brain/awf080
  • 11 Gustincich S, Manfioletti G, Del Sal G, Schneider C, Carninci P. A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques. 1991;11(3):298-300,302.
  • 12 Sen S, Burmeister M. Hardy-Weinberg analysis of a large set of published association studies reveals genotyping error and a deficit of heterozygotes across multiple loci. Hum Genomics. 2008;3(1):36-52. doi:1479-7364-3-1-36
  • 13 Clarke GM, Anderson CA, Pettersson FH, Cardon LR, Morris AP, Zondervan KT. Basic statistical analysis in genetic case-control studies. Nat Protoc. 2011;6(2):121-33. doi:10.1038/nprot.2010.182
  • 14 Yu L, Xu P, He X, Hu F, Lin Z, Zhu M et al. SNP rs7684318 of the alpha-synuclein gene is associated with Parkinson’s disease in the Han Chinese population. Brain Res. 2010;1346:262-5. doi:10.1016/j.brainres.2010.05.069
  • 15 Rubi-Castellanos R, Martínez-Cortés G, Muñoz-Valle JF, González-Martín A, Cerda-Flores RM, Anaya-Palafox M et al. Pre-Hispanic Mesoamerican demography approximates the present-day ancestry of Mestizos throughout the territory of Mexico. Am J Phys Anthropol. 2009;139(3):284-94. doi:10.1002/ajpa.20980
  • 16 Gallegos-Arreola MP, Figuera LE, Ortiz GG, Jiménez-Gil FJ, Ramírez-Vega J, Ruíz-Sandoval JL et al. Apolipoprotein E genotypes in Mexican patients with Parkinson’s disease. Dis Markers. 2009;27(5):225-30. doi:10.1155/2009/617863
  • 17 Gonzalez-Del Rincon ML, Monroy Jaramillo N, Suárez Martínez AI, Yescas Gómez P, Boll Woehrlen MC, López López M et al. The L444P GBA mutation is associated with early-onset Parkinson’s disease in Mexican Mestizos. Clin Genet. 2013;84(4):386-7. doi:10.1111/cge.12084
  • 18 Ramirez-Jirano LJ, Ruiz-Sandoval JL, Jiménez-Gil FJ, Ramírez-Vega J, Vargas-Frutos E, Gallegos-Arreola MP et al. [Frequency of the IVS4+66A-G polymorphism in the alpha-synuclein gene in patients with Parkinson’s disease in north-western Mexico]. Rev Neurol. 2007;44(1):15-7. Spanish.
  • 19 García S, López-Hernández LB, Suarez-Cuenca JA, Solano-Rojas M, Gallegos-Arreola MP, Gama-Moreno O et al. Low prevalence of most frequent pathogenic variants of six PARK genes in sporadic Parkinson’s disease. Folia Neuropathol. 2014;5(1)2:22-9. doi:10.5114/fn.2014.41741
  • 20 Yescas P, López M, Monroy N, Boll MC, Rodríguez-Violante M, Rodríguez U e t al et al. Low frequency of common LRRK2 mutations in Mexican patients with Parkinson’s disease. Neurosci Lett. 2010;485(2):79-82. doi:10.1016/j.neulet.2010.08.029
  • 21 Martínez HR, González-González H, Cantú-Martínez L, Rangel-Guerra R, Hernández-Castillo CD, Vergara-Saavedra JJ et al. PARKIN-coding polymorphisms are not associated with Parkinson’s disease in a population from northeastern Mexico. Neurosci Lett. 2010;468(3):264-6. doi:10.1016/j.neulet.2009.11.009
  • 22 Cantuti-Castelvetri I, Keller-McGandy C, Bouzou B, Asteris G, Clark TW, Frosch MP et al. Effects of gender on nigral gene expression and Parkinson disease. Neurobiol Dis. 2007;26(3):606-14. doi:10.1016/j.nbd.2007.02.009
  • 23 Frieling H, Gozner A, Römer KD, Wilhelm J, Hillemacher T, Kornhuber J et al. Alpha-synuclein mRNA levels correspond to beck depression inventory scores in females with eating disorders. Neuropsychobiology. 2008;58(1):48-52. doi:10.1159/000155991
  • 24 Frieling H Gozner A, Römer KD, Lenz B, Bönsch D, Wilhelm J et al. Global DNA hypomethylation and DNA hypermethylation of the alpha synuclein promoter in females with anorexia nervosa. Mol Psychiatry. 2007;12(3):229-30. doi:10.1038/sj.mp.4001931
  • 25 García S, Coral-Vázquez R, Gallegos-Arreola MP, Montes-Almanza LA, Canto P, García-Martínez FA et al. Association of the rs1801133 variant in the MTHFR gene and sporadic Parkinson’s disease. Folia Neuropathol. 2015;53(1):24-8. doi:10.5114/fn.2015.49971
  • 26 Jowaed A, Schmitt I, Kaut O, Wüllner U. Methylation regulates alpha-synuclein expression and is decreased in Parkinson’s disease patients’ brains. J Neurosci. 2010;30(18):6355-9. doi:10.1523/JNEUROSCI.6119-09.2010