Elizabeth Ruiz-Sánchez1, Petra Yescas2, Mayela Rodríguez-Violante3, Nancy Martínez-Rodríguez4, Jesica N Díaz-López1, Adriana Ochoa2, Sergio S Valdes-Rojas5, Daniel Magos-Rodríguez1, Julio C Rojas-Castañeda6, Amin Cervantes-Arriaga3, Samuel Canizales-Quinteros7, Patricia Rojas8. 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.
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.
Authors: Elizabeth Ruiz-Sánchez; Janet Jiménez-Genchi; Yessica M Alcántara-Flores; Carlos J Castañeda-González; Carlos L Aviña-Cervantes; Petra Yescas; María Del Socorro González-Valadez; Nancy Martínez-Rodríguez; Antonio Ríos-Ortiz; Martha González-González; María E López-Navarro; Patricia Rojas Journal: BMC Psychiatry Date: 2021-02-09 Impact factor: 3.630
Authors: Natasha de Alwis; Sally Beard; Natalie K Binder; Natasha Pritchard; Tu'uhevaha J Kaitu'u-Lino; Susan P Walker; Owen Stock; Katie M Groom; Scott Petersen; Amanda Henry; Joanne M Said; Sean Seeho; Stefan C Kane; Stephen Tong; Natalie J Hannan Journal: Sci Rep Date: 2021-10-19 Impact factor: 4.379