Yifan Zhang1, Xiongfei Wang2, Chongyang Tang2, Yuguang Guan2, Fan Chen1,3, Qing Gao1, Jing Wang3, Jian Zhou2, Feng Zhai2, Detlev Boison4, Guoming Luan2, Tianfu Li1,3. 1. 2Department of Brain Institute, Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing Key Laboratory of Epilepsy Research, Sanbo Brain Hospital, Capital Medical University, Beijing, China. 2. 1Department of Neurosurgery, Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing Key Laboratory of Epilepsy Research, Sanbo Brain Hospital, Capital Medical University, Beijing, China. 3. 3Department of Neurology, Center of Epilepsy, Beijing Institute for Brain Disorders, Sanbo Brain Hospital, Capital Medical University, Beijing, China; and. 4. 4Department of Neurosurgery, Robert Wood Johnson & New Jersey Medical Schools, Rutgers University, Piscataway, New Jersey.
Abstract
OBJECTIVE: Vagus nerve stimulation (VNS) is an alternative treatment option for individuals with refractory epilepsy, with nearly 40% of patients showing no benefit after VNS and only 6%-8% achieving seizure freedom. It is presently unclear why some patients respond to treatment and others do not. Therefore, identification of biomarkers to predict efficacy of VNS is of utmost importance. The objective of this study was to explore whether genetic variations in genes involved in adenosine kinase (ADK), ecto-5'-nucleotidase (NT5E), and adenosine A1 receptor (A1R) are linked to outcome of VNS in patients with refractory epilepsy. METHODS: Thirty single-nucleotide polymorphisms (SNPs), including 9 in genes encoding ADK, 3 in genes encoding NT5E, and 18 in genes encoding A1R, were genotyped in 194 refractory epilepsy patients who underwent VNS. The chi-square test and binary logistic regression were used to determine associations between genetic differences and VNS efficacy. RESULTS: A significant association between ADK SNPs rs11001109, rs7899674, and rs946185 and seizure reduction with VNS was found. Regardless of sex, age, seizure frequency and type, antiseizure drug use, etiology, and prior surgical history, all patients (10/10 patients [100%]) with minor allele homozygosity at rs11001109 (genotype AA) or rs946185 (AA) achieved > 50% seizure reduction and 4 patients (4/10 [40%]) achieved seizure freedom. VNS therapy demonstrated higher efficacy among carriers of minor allele rs7899674 (CG + GG) (68.3% vs 48.8% for patients with major allele homozygosity). CONCLUSIONS: Homozygous ADK SNPs rs11001109 (AA) and rs946185 (AA), as well as minor allele rs7899674 (CG + GG), may serve as useful biomarkers for prediction of VNS therapy outcome.
OBJECTIVE: Vagus nerve stimulation (VNS) is an alternative treatment option for individuals with refractory epilepsy, with nearly 40% of patients showing no benefit after VNS and only 6%-8% achieving seizure freedom. It is presently unclear why some patients respond to treatment and others do not. Therefore, identification of biomarkers to predict efficacy of VNS is of utmost importance. The objective of this study was to explore whether genetic variations in genes involved in adenosine kinase (ADK), ecto-5'-nucleotidase (NT5E), and adenosine A1 receptor (A1R) are linked to outcome of VNS in patients with refractory epilepsy. METHODS: Thirty single-nucleotide polymorphisms (SNPs), including 9 in genes encoding ADK, 3 in genes encoding NT5E, and 18 in genes encoding A1R, were genotyped in 194 refractory epilepsy patients who underwent VNS. The chi-square test and binary logistic regression were used to determine associations between genetic differences and VNS efficacy. RESULTS: A significant association between ADK SNPs rs11001109, rs7899674, and rs946185 and seizure reduction with VNS was found. Regardless of sex, age, seizure frequency and type, antiseizure drug use, etiology, and prior surgical history, all patients (10/10 patients [100%]) with minor allele homozygosity at rs11001109 (genotype AA) or rs946185 (AA) achieved > 50% seizure reduction and 4 patients (4/10 [40%]) achieved seizure freedom. VNS therapy demonstrated higher efficacy among carriers of minor allele rs7899674 (CG + GG) (68.3% vs 48.8% for patients with major allele homozygosity). CONCLUSIONS: Homozygous ADK SNPs rs11001109 (AA) and rs946185 (AA), as well as minor allele rs7899674 (CG + GG), may serve as useful biomarkers for prediction of VNS therapy outcome.