title: Promoter Variants of the ADAM10 Gene and Their Roles in Temporal Lobe Epilepsy.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hua
authors.initials: H
authors.lastname: Tao
authors.affiliation: 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.
authors.forename: Jianghao
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Clinical Research Center, Guangdong Medical University , Zhanjiang, Guangdong , China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Beijing Tongren Hospital, Capital Medical University , Beijing , China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Neurology, Central People's Hospital of Zhanjiang , Zhanjiang, Guangdong , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First People's Hospital of Pingdingshan , Pingdingshan, Hebei , China.
authors.forename: Fuhai
authors.initials: F
authors.lastname: Sun
authors.affiliation: Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Guangdong Medical University , Zhanjiang, Guangdong , China.
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Neurology, Affiliated Hospital of Guangdong Medical University , Zhanjiang, Guangdong , China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Guangdong Medical University , Zhanjiang, Guangdong , China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Guangdong Medical University , Zhanjiang, Guangdong , China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, Affiliated Hospital of Guangdong Medical University , Zhanjiang, Guangdong , China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Harbin Medical University , Harbin, Heilongjiang , China.
authors.forename: Lifen
authors.initials: L
authors.lastname: Yao
authors.affiliation: Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Guangdong Medical University , Zhanjiang, Guangdong , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Guangdong Key Laboratory of Age-related Cardiac and Cerebral Diseases, Guangdong Medical University, Zhanjiang, Guangdong, China; Jinan University, Guangzhou, Guangdong, China.
authors.forename: Keshen
authors.initials: K
authors.lastname: Li
keywords: ADAM10; epileptic seizures; promoter variants; single nucleotide polymorphisms; temporal lobe epilepsy