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J Neurol Sci. 2017 Aug 15;379:58-63. doi: 10.1016/j.jns.2017.05.029. Epub 2017 May 17.

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

Author information

1
Laboratory of Neurotoxicology, Instituto Nacional de Neurología y Neurocirugía, "Manuel Velasco Suárez", SS, Mexico City, Mexico.
2
Department of Genetics, Instituto Nacional de Neurología y Neurocirugía, "Manuel Velasco Suárez", SS, Mexico City, Mexico.
3
Clinical Neurodegenerative Research Unit, Instituto Nacional de Neurología y Neurocirugía, "Manuel Velasco Suárez", SS, Mexico City, Mexico.
4
Community Health Research Department, Hospital Infantil de México, Mexico City, Mexico.
5
Direction of Geriatric Attention, Instituto Nacional de las Personas Adultas Mayores (INAPAM), Mexico City, Mexico.
6
Laboratory of Reproductive Biology, Instituto Nacional de Pediatria, Mexico City, Mexico.
7
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-INMEGEN, Mexico.
8
Laboratory of Neurotoxicology, Instituto Nacional de Neurología y Neurocirugía, "Manuel Velasco Suárez", SS, Mexico City, Mexico. Electronic address: prcastane@hotmail.com.

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

PMID:
28716280
DOI:
10.1016/j.jns.2017.05.029
[Indexed for MEDLINE]

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