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

Stevelink, Remi, Pangilinan, Faith, Jansen, Floor E, Braun, Kees PJ, Molloy, Anne M, Brody, Lawrence C and Koeleman, Bobby PC
(2019) Assessing the genetic association between vitamin B6 metabolism and genetic generalized epilepsy. MOLECULAR GENETICS AND METABOLISM REPORTS, 21. 100518-.

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Altered vitamin B6 metabolism due to pathogenic variants in the gene <i>PNPO</i> 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 <i>PNPO</i> 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 <i>PNPO</i> 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.

Item Type: Article
Uncontrolled Keywords: Pyridoxine, GGE, GWAS, Genetics, SNP, Pharmacogenetics
Depositing User: Symplectic Admin
Date Deposited: 18 Nov 2019 10:08
Last Modified: 19 Jan 2023 00:20
DOI: 10.1016/j.ymgmr.2019.100518
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