Association of the ADORA2A receptor and CD73 polymorphisms with epilepsy

Nan-Rui Shi; Qi Wang; Jie Liu; Ji-Zhou Zhang; Bin-Lu Deng; Xiu-Min Hu; Jie Yang; Xin Wang; Xiang Chen; Yan-Qin Zuo; Ting-Ting Liu; Jia-Ling Zheng; Xin Yang; Peter Illes; Yong Tang

doi:10.3389/fphar.2023.1152667

Association of the ADORA2A receptor and CD73 polymorphisms with epilepsy

Front Pharmacol. 2023 Mar 29:14:1152667. doi: 10.3389/fphar.2023.1152667. eCollection 2023.

Authors

Nan-Rui Shi¹, Qi Wang², Jie Liu², Ji-Zhou Zhang¹, Bin-Lu Deng², Xiu-Min Hu¹, Jie Yang², Xin Wang¹, Xiang Chen², Yan-Qin Zuo¹, Ting-Ting Liu², Jia-Ling Zheng³, Xin Yang¹, Peter Illes^{1

4}, Yong Tang^{1

5}

Affiliations

¹ International Joint Research Centre on Purinergic Signalling, School of Acupuncture and Tuina/ School of Health and Rehabilitation, Chengdu University of Traditional Medicine, Chengdu, China.
² Department of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
³ School of Clinical Medicine, Chengdu University of Traditional Medicine, Chengdu, China.
⁴ Rudolf Boehm Institute for Pharmacology and Toxicology, University of Leipzig, Leipzig, Germany.
⁵ Acupuncture and Chronobiology Key Laboratory of Sichuan Province, Chengdu, China.

Abstract

Single-nucleotide polymorphisms are connected with the risk of epilepsy on occurrence, progress, and the individual response to drugs. Progress in genomic technology is exposing the complex genetic architecture of epilepsy. Compelling evidence has demonstrated that purines and adenosine are key mediators in the epileptic process. Our previous study found the interconnection of P2Y12 receptor single-nucleotide polymorphisms and epilepsy. However, little is known about the interaction between the purine nucleoside A_2A receptor and rate-limiting enzyme ecto-5'-nucleotidase/CD73 and epilepsy from the genetic polymorphism aspect. The aim of the study is to evaluate the impact of A_2AR and CD73 polymorphisms on epilepsy cases. The study group encompassed 181 patients with epilepsy and 55 healthy volunteers. A significant correlation was confirmed between CD73 rs4431401 and epilepsy (p < 0.001), with TT genotype frequency being higher and C allele being lower among epilepsy patients in comparison with healthy individuals, indicating that the presence of the TT genotype is related to an increased risk of epilepsy (OR = 2.742, p = 0.006) while carriers of the C allele demonstrated a decreased risk of epilepsy (OR = 0.304, p < 0.001). According to analysis based on gender, the allele and genotype of rs4431401 in CD73 were associated with both male and female cases (p < 0.0001, p = 0.026, respectively). Of note, we found that A2AR genetic variants rs2267076 T>C (p = 0.031), rs2298383 C>T (p = 0.045), rs4822492 T>G (p = 0.034), and rs4822489 T>G (p = 0.029) were only associated with epilepsy in female subjects instead of male. It is evident that the TT genotype and T allele of rs4431401 in CD73 were genetic risk factors for epilepsy, whereas rs2267076, rs2298383, rs4822492, and rs4822489 polymorphisms of the A_2AR were mainly associated with female subjects.

Keywords: A2A receptor; CD73; epilepsy; purinergic receptor; single-nucleotide polymorphism.

Grants and funding

This work was supported by grants from the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTDD-202003) and the Science and Technology Program of Sichuan Province, China (2022YFH0006 and 23RCYJ0059).