Ruiz-Sánchez Elizabeth, Yescas Petra, Rodríguez-Violante Mayela, 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 Patricia
Laboratory of Neurotoxicology, Instituto Nacional de Neurología y Neurocirugía, "Manuel Velasco Suárez", SS, Mexico City, Mexico.
Department of Genetics, Instituto Nacional de Neurología y Neurocirugía, "Manuel Velasco Suárez", SS, Mexico City, Mexico.
J Neurol Sci. 2017 Aug 15;379:58-63. doi: 10.1016/j.jns.2017.05.029. Epub 2017 May 17.
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.
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.
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.
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.
NR4A2转录因子在多巴胺能神经元的发育、存活和表型中起着重要作用，并且被认为是帕金森病（PD）的一种可能的生物标志物。因此，我们的目的是在一组患有特发性PD的墨西哥人群样本中分析NR4A2基因的突变（在两个热点突变区域）和两个多态性（启动子区域的rs34884856和内含子区域的rs35479735）。我们还评估了墨西哥人群外周血中NR4A2基因的表达水平，并确定它们是否与NR4A2基因多态性相关。
我们进行了一项病例对照研究，其中包括227例特发性PD病例和454例无关对照。通过高分辨率熔解（HRM）对NR4A2基因的遗传变异进行基因分型，并通过自动测序方法进行验证。使用实时聚合酶链反应在外周血中进行基因表达分析。
rs35479735多态性与患PD的较高风险相关。此外，PD患者中NR4A2基因表达显著降低。连锁不平衡分析显示单倍型H4（3C - 3G）表达水平较低，并且包含两种多态性的风险等位基因。
总之，这是在墨西哥人群中首次考虑对PD患者进行NR4A2分析的研究。在PD患者中鉴定出NR4A2的基因型与mRNA表达水平之间存在关联。这些结果表明，NR4A2基因的多态性和表达可能在墨西哥人群患PD的风险中起重要作用。
