Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders

Version 1 : Received: 21 July 2023 / Approved: 21 July 2023 / Online: 21 July 2023 (13:20:04 CEST)

A peer-reviewed article of this Preprint also exists.

Martínez-Iglesias, O.; Naidoo, V.; Carrera, I.; Carril, J.C.; Cacabelos, N.; Cacabelos, R. Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders. Biology 2023, 12, 1156. Martínez-Iglesias, O.; Naidoo, V.; Carrera, I.; Carril, J.C.; Cacabelos, N.; Cacabelos, R. Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders. Biology 2023, 12, 1156.

Abstract

Pharmacogenetics and DNA methylation influence therapeutic outcomes and provide insights into potential therapeutic targets for brain-related disorders. To understand the effect of genetic polymorphisms on drug response and disease risk, we analyzed the relationship between global DNA methylation, drug-metabolizing enzymes, transport genes, and pathogenic gene phenotypes in serum samples from two groups of patients: Group A, which showed increased 5-methylcytosine (5mC) levels during clinical follow-up, and Group B, which exhibited no discernible change in 5mC levels. We identified specific SNPs in several metabolizing genes, including CYP1A2, CYP2C9, CYP4F2, GSTP1, and NAT2 that were associated with differential drug responses. Specific SNPs in CYP had a significant impact on enzyme activity, leading to changes in phenotypic distribution between the two patient groups. Group B, which contained a lower frequency of normal metabolizers and a higher frequency of ultra-rapid metabolizers compared to patients in Group A, did not show an improvement in 5mC levels during follow-up. Furthermore, there were significant differences in phenotype distribution between patient Groups A and B for several SNPs associated with transporter genes (ABCB1, ABCC2, SLC2A9, SLC39A8, and SLCO1B1) and pathogenic genes (APOE, NBEA, and PTGS2). These findings appear to suggest that the interplay between pharmacogenomics and DNA methylation has important implications for improving treatment outcomes in patients with brain-related disorders.

Keywords

Epigenetics; DNA methylation; Pharmacogenetics; Neurological Disorders

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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