Association of polymorphisms and reduced expression levels of the NR4A2 gene with Parkinson's disease in a Mexican population

Elizabeth Ruiz-Sánchez, Petra Yescas, Mayela De jesus Rodriguez Violante, Nancy Martínez-Rodríguez, Jesica N. Díaz-López, Adriana Ochoa, Sergio S. Valdes-Rojas, Daniel Magos-Rodríguez, Julio C. Rojas-Castañeda, Amin Cervantes-Arriaga, Samuel Canizales-Quinteros, Patricia Rojas Castañeda

Resultado de la investigación: Contribución a una revistaArtículo

Resumen

Introduction The NR4A2 transcription factor is important in the development, survival and phenotype of dopaminergic neurons and it is postulated as a possible biomarker for Parkinson's disease (PD). Therefore, our aim was to analyze in a sample of a Mexican population with idiopathic PD, mutations (in two hotspot mutation regions) and two polymorphisms (rs34884856 in promotor and rs35479735 intronic regions) of the NR4A2 gene. We also evaluate the levels of NR4A2 gene expression in peripheral blood for a Mexican population, and identify whether they are associated with NR4A2 gene polymorphisms. Methods We conducted a case-control study, which included 227 idiopathic PD cases and 454 unrelated controls. Genetic variants of the NR4A2 gene were genotyped by high-resolution melting (HRM) and validated by an automated sequencing method. The gene expression was performed in peripheral blood using a real-time polymerase chain reaction. Results The rs35479735 polymorphism was associated with a higher risk of developing PD. In addition, NR4A2 gene expression was significantly decreased in patients with PD. Linkage disequilibrium analysis showed a haplotype H4 (3C-3G) that showed lower levels of expression, and contained the risk alleles for both polymorphisms. Conclusions In summary, this is the first study in a Mexican population that considers the analysis of NR4A2 in patients with PD. An association was identified between genotype and mRNA expression levels of NR4A2 in patients with PD. These results suggest that polymorphisms and expression of the NR4A2 gene could play an important role in the risk of developing PD in Mexican populations.

Idioma originalInglés
Páginas (desde-hasta)58-63
Número de páginas6
PublicaciónJournal of the Neurological Sciences
Volumen379
DOI
EstadoPublicada - 15 ago 2017

Huella dactilar

Parkinson Disease
Population
Genes
Gene Expression
Mutation
Dopaminergic Neurons
Linkage Disequilibrium
Haplotypes
Freezing
Case-Control Studies
Real-Time Polymerase Chain Reaction
Transcription Factors
Biomarkers
Alleles
Genotype
Phenotype
Messenger RNA
Survival

Citar esto

Ruiz-Sánchez, Elizabeth ; Yescas, Petra ; Rodriguez Violante, Mayela De jesus ; Martínez-Rodríguez, Nancy ; Díaz-López, Jesica N. ; Ochoa, Adriana ; Valdes-Rojas, Sergio S. ; Magos-Rodríguez, Daniel ; Rojas-Castañeda, Julio C. ; Cervantes-Arriaga, Amin ; Canizales-Quinteros, Samuel ; Rojas Castañeda, Patricia. / Association of polymorphisms and reduced expression levels of the NR4A2 gene with Parkinson's disease in a Mexican population. En: Journal of the Neurological Sciences. 2017 ; Vol. 379. pp. 58-63.
@article{5055004008434f558d2da3ec5d02f088,
title = "Association of polymorphisms and reduced expression levels of the NR4A2 gene with Parkinson's disease in a Mexican population",
abstract = "Introduction The NR4A2 transcription factor is important in the development, survival and phenotype of dopaminergic neurons and it is postulated as a possible biomarker for Parkinson's disease (PD). Therefore, our aim was to analyze in a sample of a Mexican population with idiopathic PD, mutations (in two hotspot mutation regions) and two polymorphisms (rs34884856 in promotor and rs35479735 intronic regions) of the NR4A2 gene. We also evaluate the levels of NR4A2 gene expression in peripheral blood for a Mexican population, and identify whether they are associated with NR4A2 gene polymorphisms. Methods We conducted a case-control study, which included 227 idiopathic PD cases and 454 unrelated controls. Genetic variants of the NR4A2 gene were genotyped by high-resolution melting (HRM) and validated by an automated sequencing method. The gene expression was performed in peripheral blood using a real-time polymerase chain reaction. Results The rs35479735 polymorphism was associated with a higher risk of developing PD. In addition, NR4A2 gene expression was significantly decreased in patients with PD. Linkage disequilibrium analysis showed a haplotype H4 (3C-3G) that showed lower levels of expression, and contained the risk alleles for both polymorphisms. Conclusions In summary, this is the first study in a Mexican population that considers the analysis of NR4A2 in patients with PD. An association was identified between genotype and mRNA expression levels of NR4A2 in patients with PD. These results suggest that polymorphisms and expression of the NR4A2 gene could play an important role in the risk of developing PD in Mexican populations.",
keywords = "Association, Genetics, NR4A2 gene, Parkinson's disease, Polymorphisms",
author = "Elizabeth Ruiz-S{\'a}nchez and Petra Yescas and {Rodriguez Violante}, {Mayela De jesus} and Nancy Mart{\'i}nez-Rodr{\'i}guez and D{\'i}az-L{\'o}pez, {Jesica N.} and Adriana Ochoa and Valdes-Rojas, {Sergio S.} and Daniel Magos-Rodr{\'i}guez and Rojas-Casta{\~n}eda, {Julio C.} and Amin Cervantes-Arriaga and Samuel Canizales-Quinteros and {Rojas Casta{\~n}eda}, Patricia",
year = "2017",
month = "8",
day = "15",
doi = "10.1016/j.jns.2017.05.029",
language = "Ingl{\'e}s",
volume = "379",
pages = "58--63",
journal = "Journal of the Neurological Sciences",
issn = "0022-510X",
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Ruiz-Sánchez, E, Yescas, P, Rodriguez Violante, MDJ, Martínez-Rodríguez, N, Díaz-López, JN, Ochoa, A, Valdes-Rojas, SS, Magos-Rodríguez, D, Rojas-Castañeda, JC, Cervantes-Arriaga, A, Canizales-Quinteros, S & Rojas Castañeda, P 2017, 'Association of polymorphisms and reduced expression levels of the NR4A2 gene with Parkinson's disease in a Mexican population', Journal of the Neurological Sciences, vol. 379, pp. 58-63. https://doi.org/10.1016/j.jns.2017.05.029

Association of polymorphisms and reduced expression levels of the NR4A2 gene with Parkinson's disease in a Mexican population. / Ruiz-Sánchez, Elizabeth; Yescas, Petra; Rodriguez Violante, Mayela De jesus; Martínez-Rodríguez, Nancy; Díaz-López, Jesica N.; Ochoa, Adriana; Valdes-Rojas, Sergio S.; Magos-Rodríguez, Daniel; Rojas-Castañeda, Julio C.; Cervantes-Arriaga, Amin; Canizales-Quinteros, Samuel; Rojas Castañeda, Patricia.

En: Journal of the Neurological Sciences, Vol. 379, 15.08.2017, p. 58-63.

Resultado de la investigación: Contribución a una revistaArtículo

TY - JOUR

T1 - Association of polymorphisms and reduced expression levels of the NR4A2 gene with Parkinson's disease in a Mexican population

AU - Ruiz-Sánchez, Elizabeth

AU - Yescas, Petra

AU - Rodriguez Violante, Mayela De jesus

AU - Martínez-Rodríguez, Nancy

AU - Díaz-López, Jesica N.

AU - Ochoa, Adriana

AU - Valdes-Rojas, Sergio S.

AU - Magos-Rodríguez, Daniel

AU - Rojas-Castañeda, Julio C.

AU - Cervantes-Arriaga, Amin

AU - Canizales-Quinteros, Samuel

AU - Rojas Castañeda, Patricia

PY - 2017/8/15

Y1 - 2017/8/15

N2 - Introduction The NR4A2 transcription factor is important in the development, survival and phenotype of dopaminergic neurons and it is postulated as a possible biomarker for Parkinson's disease (PD). Therefore, our aim was to analyze in a sample of a Mexican population with idiopathic PD, mutations (in two hotspot mutation regions) and two polymorphisms (rs34884856 in promotor and rs35479735 intronic regions) of the NR4A2 gene. We also evaluate the levels of NR4A2 gene expression in peripheral blood for a Mexican population, and identify whether they are associated with NR4A2 gene polymorphisms. Methods We conducted a case-control study, which included 227 idiopathic PD cases and 454 unrelated controls. Genetic variants of the NR4A2 gene were genotyped by high-resolution melting (HRM) and validated by an automated sequencing method. The gene expression was performed in peripheral blood using a real-time polymerase chain reaction. Results The rs35479735 polymorphism was associated with a higher risk of developing PD. In addition, NR4A2 gene expression was significantly decreased in patients with PD. Linkage disequilibrium analysis showed a haplotype H4 (3C-3G) that showed lower levels of expression, and contained the risk alleles for both polymorphisms. Conclusions In summary, this is the first study in a Mexican population that considers the analysis of NR4A2 in patients with PD. An association was identified between genotype and mRNA expression levels of NR4A2 in patients with PD. These results suggest that polymorphisms and expression of the NR4A2 gene could play an important role in the risk of developing PD in Mexican populations.

AB - Introduction The NR4A2 transcription factor is important in the development, survival and phenotype of dopaminergic neurons and it is postulated as a possible biomarker for Parkinson's disease (PD). Therefore, our aim was to analyze in a sample of a Mexican population with idiopathic PD, mutations (in two hotspot mutation regions) and two polymorphisms (rs34884856 in promotor and rs35479735 intronic regions) of the NR4A2 gene. We also evaluate the levels of NR4A2 gene expression in peripheral blood for a Mexican population, and identify whether they are associated with NR4A2 gene polymorphisms. Methods We conducted a case-control study, which included 227 idiopathic PD cases and 454 unrelated controls. Genetic variants of the NR4A2 gene were genotyped by high-resolution melting (HRM) and validated by an automated sequencing method. The gene expression was performed in peripheral blood using a real-time polymerase chain reaction. Results The rs35479735 polymorphism was associated with a higher risk of developing PD. In addition, NR4A2 gene expression was significantly decreased in patients with PD. Linkage disequilibrium analysis showed a haplotype H4 (3C-3G) that showed lower levels of expression, and contained the risk alleles for both polymorphisms. Conclusions In summary, this is the first study in a Mexican population that considers the analysis of NR4A2 in patients with PD. An association was identified between genotype and mRNA expression levels of NR4A2 in patients with PD. These results suggest that polymorphisms and expression of the NR4A2 gene could play an important role in the risk of developing PD in Mexican populations.

KW - Association

KW - Genetics

KW - NR4A2 gene

KW - Parkinson's disease

KW - Polymorphisms

UR - http://www.scopus.com/inward/record.url?scp=85020044274&partnerID=8YFLogxK

U2 - 10.1016/j.jns.2017.05.029

DO - 10.1016/j.jns.2017.05.029

M3 - Artículo

C2 - 28716280

AN - SCOPUS:85020044274

VL - 379

SP - 58

EP - 63

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

SN - 0022-510X

ER -