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Article: Assessing the genetic association between vitamin B6 metabolism and genetic generalized epilepsy

TitleAssessing the genetic association between vitamin B6 metabolism and genetic generalized epilepsy
Authors
KeywordsPyridoxine
GGE
GWAS
Genetics
SNP
Issue Date2019
PublisherElsevier: Open Access Journals. The Journal's web site is located at http://www.sciencedirect.com/science/journal/22144269
Citation
Molecular Genetics and Metabolism Reports, 2019, v. 21, p. article no. 100518 How to Cite?
AbstractAltered vitamin B6 metabolism due to pathogenic variants in the gene PNPO causes early onset epileptic encephalopathy, which can be treated with high doses of vitamin B6. We recently reported that single nucleotide polymorphisms (SNPs) that influence PNPO expression in the brain are associated with genetic generalized epilepsy (GGE). However, it is not known whether any of these GGE-associated SNPs influence vitamin B6 metabolite levels. Such an influence would suggest that vitamin B6 could play a role in GGE therapy. Here, we performed genome-wide association studies (GWAS) to assess the influence of GGE associated genetic variants on measures of vitamin B6 metabolism in blood plasma in 2232 healthy individuals. We also asked if SNPs that influence vitamin B6 were associated with GGE in 3122 affected individuals and 20,244 controls. Our GWAS of vitamin B6 metabolites reproduced a previous association and found a novel genome-wide significant locus. The SNPs in these loci were not associated with GGE. We found that 84 GGE-associated SNPs influence expression levels of PNPO in the brain as well as in blood. However, these SNPs were not associated with vitamin B6 metabolism in plasma. By leveraging polygenic risk scoring (PRS), we found suggestive evidence of higher catabolism and lower levels of the active and transport forms of vitamin B6 in GGE, although these findings require further replication.
Persistent Identifierhttp://hdl.handle.net/10722/308332
ISSN
2023 Impact Factor: 1.8
2023 SCImago Journal Rankings: 0.639
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorStevelink, R-
dc.contributor.authorPangilinan, F-
dc.contributor.authorJansen, FE-
dc.contributor.authorBraun, KPJ-
dc.contributor.authorInternational League Against Epilepsy Consortium on Complex Epilepsies-
dc.contributor.authorBaum, L-
dc.contributor.authorYang, W-
dc.contributor.authorMolloy, AM-
dc.contributor.authorBrody, LC-
dc.contributor.authorKoeleman, BPC-
dc.date.accessioned2021-11-25T03:20:58Z-
dc.date.available2021-11-25T03:20:58Z-
dc.date.issued2019-
dc.identifier.citationMolecular Genetics and Metabolism Reports, 2019, v. 21, p. article no. 100518-
dc.identifier.issn2214-4269-
dc.identifier.urihttp://hdl.handle.net/10722/308332-
dc.description.abstractAltered vitamin B6 metabolism due to pathogenic variants in the gene PNPO causes early onset epileptic encephalopathy, which can be treated with high doses of vitamin B6. We recently reported that single nucleotide polymorphisms (SNPs) that influence PNPO expression in the brain are associated with genetic generalized epilepsy (GGE). However, it is not known whether any of these GGE-associated SNPs influence vitamin B6 metabolite levels. Such an influence would suggest that vitamin B6 could play a role in GGE therapy. Here, we performed genome-wide association studies (GWAS) to assess the influence of GGE associated genetic variants on measures of vitamin B6 metabolism in blood plasma in 2232 healthy individuals. We also asked if SNPs that influence vitamin B6 were associated with GGE in 3122 affected individuals and 20,244 controls. Our GWAS of vitamin B6 metabolites reproduced a previous association and found a novel genome-wide significant locus. The SNPs in these loci were not associated with GGE. We found that 84 GGE-associated SNPs influence expression levels of PNPO in the brain as well as in blood. However, these SNPs were not associated with vitamin B6 metabolism in plasma. By leveraging polygenic risk scoring (PRS), we found suggestive evidence of higher catabolism and lower levels of the active and transport forms of vitamin B6 in GGE, although these findings require further replication.-
dc.languageeng-
dc.publisherElsevier: Open Access Journals. The Journal's web site is located at http://www.sciencedirect.com/science/journal/22144269-
dc.relation.ispartofMolecular Genetics and Metabolism Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectPyridoxine-
dc.subjectGGE-
dc.subjectGWAS-
dc.subjectGenetics-
dc.subjectSNP-
dc.titleAssessing the genetic association between vitamin B6 metabolism and genetic generalized epilepsy-
dc.typeArticle-
dc.identifier.emailYang, W: yangwl@hkucc.hku.hk-
dc.identifier.authorityYang, W=rp00524-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.ymgmr.2019.100518-
dc.identifier.pmid31641590-
dc.identifier.pmcidPMC6796782-
dc.identifier.scopuseid_2-s2.0-85073031958-
dc.identifier.hkuros314620-
dc.identifier.volume21-
dc.identifier.spagearticle no. 100518-
dc.identifier.epagearticle no. 100518-
dc.identifier.isiWOS:000500718300012-
dc.publisher.placeNetherlands-

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