Genetic Polymorphism of ADORA2A Is Associated With the Risk of Epilepsy and Predisposition to Neurologic Comorbidity in Chinese Southern Children

Abstract

Epilepsy, a common disorder of the brain, exhibits a high morbidity rate in children. Childhood epilepsy (CE) is frequently comorbid with neurologic and developmental disorders, sharing underlying genetic factors. This study aimed to investigate the impact of ADORA2A , BDNF , and NTRK2 gene polymorphisms on the risk of childhood epilepsy and their associations with predisposition to epileptic comorbidities. A total of 444 children were enrolled in this study, and three single nucleotide polymorphisms, including ADORA2A rs2298383, BDNF rs6265, and NTRK2 rs1778929, were genotyped. The frequency distribution of genotypes was compared not only between CE patients and healthy children but also between CE patients with and without comorbidities. The results indicated that the carriers of ADORA2A rs2298383 TT genotype tended to have a lower risk of epilepsy (OR = 0.48, 95% CI = 0.30–0.76), while the CT genotype was related to a higher risk (OR = 1.56, 95% CI = 1.06–2.27). The ADORA2A rs2298383 CC genotype predisposed CE patients to comorbid neurologic disorders (OR = 2.76, 95% CI = 1.31–5.80). Genetic variations in BDNF rs6265 and NTRK2 rs1778929 had no significant association with CE and its comorbidities. Fourteen ADORA2A target genes related to epilepsy were identified by the protein–protein interaction analysis, which were mainly involved in the biological processes of “negative regulation of neuron death” and “purine nucleoside biosynthetic process” through the gene functional enrichment analysis. Our study revealed that the genetic polymorphism of ADORA2A rs2298383 was associated with CE risk and predisposition to neurologic comorbidity in children with epilepsy, and the involved mechanism might be related to the regulation of neuron death and purine nucleoside biosynthesis.

Genetic Polymorphisms, Gene–Gene Interactions and Neurologic Sequelae at Two Years Follow-Up in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia

“…To the best of our knowledge, our study was the first to evaluate the role of genetic variability and the risk of epilepsy after HIE in newborns treated with TH. Some studies have already been performed regarding polymorphisms and the risk of epilepsy [ 23 , 57 , 58 , 59 ], but none of them investigated epilepsy after HIE treated with TH separately from other epilepsy causes.…”

AS3MT Polymorphism: A Risk Factor for Epilepsy Susceptibility and Adverse Drug Reactions to Valproic Acid and Oxcarbazepine Treatment in Children From South China

“…Values with p < 0.05 were considered statistically significant. The power of this study for the minimum sample size calculation was computed for verification as described in our previous study (Fan et al, 2020). Power > 0.9 was obtained based on the frequency distribution of three AS3MT rs7085104 genotypes from participants in the control and case groups.…”

“…Pediatric patients with epilepsy (n = 200) and healthy individuals (n = 244) of Han Chinese descent from Shenzhen Baoan Women's and Children's Health Hospital were enrolled into this case-control study as described previously (Fan et al, 2020). All participants or their parents signed an informed consent approved by Baoan Women's and Children's Health Hospital ethics committee.…”

Genetic Polymorphism of GABRG2 rs211037 is Associated with Drug Response and Adverse Drug Reactions to Valproic Acid in Chinese Southern Children with Epilepsy

“…The polymerase chain reaction was performed as described in detail in our previous study. 29 Genotyping of GABRG2 rs211037 was carried out using iPLEX ® Gold Assay and Sequenom MassArray System (Agena Bioscience, San Diego, CA, United States). The MassArray Typer 4.0 software was used for data acquisition and analysis.…”

“…Genes with a relevance score ≥1 were selected in GeneCards database, and those with PubMed IDs >0 were included in DisGeNET database. 29 Genes associated with VPA were obtained from GeneCards and DrugBank, and the overlapping genes were removed. All the ADR-related genes from the above two databases and VPA-associated genes were both intersected with the genes related to GABRG2 from PPI analysis, and GABRG2 -associated target genes in VPA-induced ADRs were obtained.…”