Shi Nan-Rui, Wang Qi, Liu Jie, Zhang Ji-Zhou, Deng Bin-Lu, Hu Xiu-Min, Yang Jie, Wang Xin, Chen Xiang, Zuo Yan-Qin, Liu Ting-Ting, Zheng Jia-Ling, Yang Xin, Illes Peter, Tang Yong
International Joint Research Centre on Purinergic Signalling, School of Acupuncture and Tuina/ School of Health and Rehabilitation, Chengdu University of Traditional Medicine, Chengdu, China.
Department of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Front Pharmacol. 2023 Mar 29;14:1152667. doi: 10.3389/fphar.2023.1152667. eCollection 2023.
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 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 AR 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 ( < 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, = 0.006) while carriers of the C allele demonstrated a decreased risk of epilepsy (OR = 0.304, < 0.001). According to analysis based on gender, the allele and genotype of rs4431401 in CD73 were associated with both male and female cases ( < 0.0001, = 0.026, respectively). Of note, we found that A2AR genetic variants rs2267076 T>C ( = 0.031), rs2298383 C>T ( = 0.045), rs4822492 T>G ( = 0.034), and rs4822489 T>G ( = 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 AR were mainly associated with female subjects.
单核苷酸多态性与癫痫的发生、发展以及个体对药物的反应风险相关。基因组技术的进步正在揭示癫痫复杂的遗传结构。有力证据表明，嘌呤和腺苷是癫痫过程中的关键介质。我们之前的研究发现了P2Y12受体单核苷酸多态性与癫痫之间的联系。然而，从基因多态性方面来看，关于嘌呤核苷A受体与限速酶胞外5'-核苷酸酶/CD73之间的相互作用以及与癫痫的关系，人们了解甚少。本研究的目的是评估AR和CD73多态性对癫痫病例的影响。研究组包括181例癫痫患者和55名健康志愿者。证实CD73 rs4431401与癫痫之间存在显著相关性（<0.001），与健康个体相比，癫痫患者中TT基因型频率更高，C等位基因频率更低，这表明TT基因型的存在与癫痫风险增加相关（OR = 2.742， = 0.006），而C等位基因携带者的癫痫风险降低（OR = 0.304，<0.001）。根据基于性别的分析，CD73中rs4431401的等位基因和基因型与男性和女性病例均相关（分别为<0.0001， = 0.026）。值得注意的是，我们发现A2AR基因变异rs2267076 T>C（ = 0.031）、rs2298383 C>T（ = 0.045）、rs4822492 T>G（ = 0.034）和rs4822489 T>G（ = 0.029）仅与女性受试者的癫痫相关，而与男性无关。显然，CD73中rs4431401的TT基因型和T等位基因是癫痫的遗传危险因素，而AR的rs2267076、rs2298383、rs4822492和rs4822489多态性主要与女性受试者相关。
