Polymorphisms in the receptor for advanced glycation end products gene are associated with susceptibility to drug-resistant epilepsy

• Published in: Neuroscience letters 2016-04, Vol.619, p.137-141
• Main Authors: Guo, Mingxing, Wang, Jiafeng, Qi, Huili, Liu, Fei, Yao, Lifen, Zhang, Shuyan, Li, Keshen
• Format: Article
• Language: English
• Subjects: Asian Continental Ancestry Group; Association study; Case-Control Studies; Epilepsy; Epilepsy - drug therapy; Epilepsy - ethnology; Epilepsy - genetics; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; RAGE; Receptor for Advanced Glycation End Products - genetics; Single nucleotide polymorphism; Treatment Failure
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2016.01.043

•We identified the associations between the RAGE polymorphisms and epilepsy (EP).•A novel association between genetic variant in the RAGE G82S locus and EP was found.•The 82S+ genotype/allele were more common in drug-resistant epilepsy (DRE) patients.•The haplotype T-A-A exhibited different frequencies between DRE and controls.•The GS genotype of the G82S locus is a risk factor for DRE in Chinese population. Increasing evidence has demonstrated that inflammation plays an important role in epilepsy (EP). As a cell-surface molecule of the immunoglobulin superfamily, the receptor for advanced glycation end products (RAGE) is involved in inflammation-related disease. Functional polymorphisms in the regulatory elements and/or ligand-binding regions of RAGE may alter the expression and function of RAGE, thus affecting EP susceptibility. Here, we have identified a novel association between genetic variants in the RAGE G82S locus and EP (p=0.033) using a case-control study in a Chinese population. Further analyses showed that the 82S+ genotype and S allele were more common in patients with drug-resistant epilepsy (DRE) than in those with drug-responsive EP compared with controls. The loci -374T/A and -429T/C did not demonstrate any association with EP, but the haplotype T-A-A exhibited significantly different frequencies between DRE patients and controls (OR=1.696, 95% CI: 1.188–2.420, P=0.003). Our study provides preliminary evidence that the G82S polymorphism in RAGE is associated with increased DRE risk and that the GS genotype of the G82S locus is a risk factor for DRE in the Chinese population.