Tao Hua, Zhao Jianghao, Zhou Xu, Ma Zhonghua, Chen Ying, Sun Fuhai, Cui Lili, Zhou Haihong, Cai Yujie, Chen Yanyan, Zhao Shu, Yao Lifen, Zhao Bin, Li Keshen
Department of Neurology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China; Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Guangdong Medical University, Zhanjiang, Guangdong, China.
Clinical Research Center, Guangdong Medical University , Zhanjiang, Guangdong , China.
Front Neurol. 2016 Jun 30;7:108. doi: 10.3389/fneur.2016.00108. eCollection 2016.
Previous evidence has indicated that downregulated ADAM10 gives rise to epileptic seizures in Alzheimer's disease, and this study investigated the association of ADAM10 with temporal lobe epilepsy (TLE) from a genetic perspective. A total of 496 TLE patients and 528 healthy individuals were enrolled and genotyped for ADAM10 promoter variants (rs653765 G > A and rs514049 A > C). The alleles, genotypes, and haplotypes were then compared with clarify the association of these variants with TLE and their impacts upon age at onset, initial seizure types before treatments, and responses to drug treatments. In cohorts I, II, and I + II, the frequencies of the A allele and AA genotype at rs514049 were consistently increased in the cases compared with the controls (p = 0.020 and p = 0.009; p = 0.008 and p = 0.009; p = 0.000 and p = 0.000; q = 0.003 and q = 0.002, respectively). In contrast, the frequency of the AC haplotype (rs653765-rs514049) decreased in cohorts I + II (p = 0.013). Further analyses of the TLE patients indicated that the AA genotype functioned as a predisposing factor to drug-resistant TLE and the AC haplotype as a protective factor against generalized tonic-clonic seizures (GTCS) and drug-resistant TLE. This study is the first to demonstrate an association of the ADAM10 promoter variants with TLE. In particular, the AA genotype and AC haplotype showed their effects upon GTCS and drug-resistant TLE.
先前的证据表明，ADAM10表达下调会引发阿尔茨海默病中的癫痫发作，本研究从遗传学角度调查了ADAM10与颞叶癫痫（TLE）的关联。共纳入496例TLE患者和528名健康个体，对ADAM10启动子变体（rs653765 G＞A和rs514049 A＞C）进行基因分型。然后比较等位基因、基因型和单倍型，以阐明这些变体与TLE的关联及其对发病年龄、治疗前初始发作类型和药物治疗反应的影响。在队列I、II和I + II中，与对照组相比，rs514049位点的A等位基因和AA基因型频率在病例组中持续增加（p = 0.020和p = 0.009；p = 0.008和p = 0.009；p = 0.000和p = 0.000；q分别为0.003和0.002）。相比之下，在队列I + II中，AC单倍型（rs653765 - rs514049）的频率降低（p = 0.013）。对TLE患者的进一步分析表明，AA基因型是耐药性TLE的易感因素，而AC单倍型是预防全身强直阵挛性发作（GTCS）和耐药性TLE的保护因素。本研究首次证明ADAM10启动子变体与TLE有关联。特别是，AA基因型和AC单倍型显示出它们对GTCS和耐药性TLE的影响。
