{"id":36019,"date":"2025-04-20T16:27:09","date_gmt":"2025-04-20T16:27:09","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/36019\/"},"modified":"2025-04-20T16:27:09","modified_gmt":"2025-04-20T16:27:09","slug":"epilepsy-drug-resistance-linked-to-genetic-variants","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/36019\/","title":{"rendered":"Epilepsy Drug Resistance Linked to Genetic Variants"},"content":{"rendered":"

\"BrainCredit: KATERYNA KON\/SCIENCE PHOTO LIBRARY\/Getty Images<\/p>\n

People with focal epilepsy who are resistant to available medications may be carriers of common genetic variants that impact the efficacy of these drugs.<\/p>\n

Focal epilepsy, which starts in a specific area of the brain, is the most common form of the neurological condition (61% of cases), affecting around 4 people in every 1,000. Although anti-seizure medications are available, they only work for two-thirds of people with this type of epilepsy.<\/p>\n

\u201cPrior studies, although inconclusive, suggested the involvement of common genetic variants in drug response and a potential heritable component to drug resistance in epilepsy,\u201d wrote Sanjay Sisodiya, PhD, a professor at University College London, and colleagues in eBioMedicine<\/a>.<\/p>\n

\u201cThis study provides evidence for common genetic variants associated with drug response in focal epilepsy, confirming these earlier suggestions.\u201d<\/p>\n

The researchers carried out a genome-wide association study in two epilepsy cohorts, EpiPGX and Epi25, with European ancestry. Overall, there were 4,208 drug-resistant and 2,618 drug-responsive patients in the group.<\/p>\n

They found that seven single nucleotide polymorphisms in an area on chromosome 1 that included the genes CNIH4, WDR26, and CNIH3, were linked to protection against drug resistance.\u00a0In addition, overexpression of the genes CNIH3 and WDR26 was seen in people with drug-resistant epilepsy compared with individuals who responded to treatment.<\/p>\n

\u201cPathogenic variants in WDR26 have been shown to cause a drug-responsive seizure phenotype consistent with the protective effect observed in our meta-analysis and the higher expression levels in drug-resistant cases suggested by our transcriptome-wide association study,\u201d wrote the authors.\u00a0\u201cCNIH3 acts as an auxiliary subunit that regulates AMPA receptor gating and trafficking, and abnormal AMPA receptor trafficking could contribute to seizure activity,\u201d they added.<\/p>\n

The researchers need to further validate their findings before they can be used in patients, but believe they could help identify people who may develop drug resistance to epilepsy medications at an early stage and also help develop new medications for these patients.<\/p>\n

\u201cOur study provides the first evidence that common genetic variants\u2014usually not addressed in clinical genetic testing\u2014significantly contribute to drug resistance in epilepsy,\u201d said first author of the study, Costin Leu, PhD, a researcher at UTHealth Houston, in a press statement.<\/p>\n

\u201cRecognizing these genetic variants, which are frequent in the general population yet strongly influence treatment outcomes, underscores the need to expand genetic testing and future therapies to address polygenic epilepsy, a type of epilepsy that is influenced by multiple genes.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"Credit: KATERYNA KON\/SCIENCE PHOTO LIBRARY\/Getty Images People with focal epilepsy who are resistant to available medications may be…\n","protected":false},"author":2,"featured_media":36020,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3846],"tags":[20775,11022,14951,267,11921,20776,11922,14949,11923,70,11920,20774,16,15],"class_list":{"0":"post-36019","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-antiepileptics","9":"tag-epilepsy","10":"tag-genetic-variants","11":"tag-genetics","12":"tag-molecular-dx","13":"tag-multidrug-resistance","14":"tag-news-features","15":"tag-patient-care","16":"tag-precision-medicine","17":"tag-science","18":"tag-topics","19":"tag-translational-research","20":"tag-uk","21":"tag-united-kingdom"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/114371234746741480","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/36019","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=36019"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/36019\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/36020"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=36019"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=36019"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=36019"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}