Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders
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, d...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-7737/12/9/1156 |
| _version_ | 1797581220641505280 |
|---|---|
| author | Olaia Martínez-Iglesias Vinogran Naidoo Iván Carrera Juan Carlos Carril Natalia Cacabelos Ramón Cacabelos |
| author_facet | Olaia Martínez-Iglesias Vinogran Naidoo Iván Carrera Juan Carlos Carril Natalia Cacabelos Ramón Cacabelos |
| author_sort | Olaia Martínez-Iglesias |
| collection | DOAJ |
| description | 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 <i>CYP1A2</i>, <i>CYP2C9</i>, <i>CYP4F2</i>, <i>GSTP1</i>, and <i>NAT2</i>, 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 (<i>ABCB1</i>, <i>ABCC2</i>, <i>SLC2A9</i>, <i>SLC39A8</i>, and <i>SLCO1B1</i>) and pathogenic genes (<i>APOE</i>, <i>NBEA</i>, and <i>PTGS2</i>). 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. |
| first_indexed | 2024-03-10T23:01:13Z |
| format | Article |
| id | doaj.art-394262e825fd48948614e827b8efe2c0 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T23:01:13Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-394262e825fd48948614e827b8efe2c02023-11-19T09:37:50ZengMDPI AGBiology2079-77372023-08-01129115610.3390/biology12091156Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological DisordersOlaia Martínez-Iglesias0Vinogran Naidoo1Iván Carrera2Juan Carlos Carril3Natalia Cacabelos4Ramón Cacabelos5EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Bergondo, Corunna, SpainEuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Bergondo, Corunna, SpainEuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Bergondo, Corunna, SpainEuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Bergondo, Corunna, SpainEuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Bergondo, Corunna, SpainEuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Bergondo, Corunna, SpainPharmacogenetics 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 <i>CYP1A2</i>, <i>CYP2C9</i>, <i>CYP4F2</i>, <i>GSTP1</i>, and <i>NAT2</i>, 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 (<i>ABCB1</i>, <i>ABCC2</i>, <i>SLC2A9</i>, <i>SLC39A8</i>, and <i>SLCO1B1</i>) and pathogenic genes (<i>APOE</i>, <i>NBEA</i>, and <i>PTGS2</i>). 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.https://www.mdpi.com/2079-7737/12/9/1156epigeneticsDNA methylationpharmacogeneticsneurological disorders |
| spellingShingle | Olaia Martínez-Iglesias Vinogran Naidoo Iván Carrera Juan Carlos Carril Natalia Cacabelos Ramón Cacabelos Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders Biology epigenetics DNA methylation pharmacogenetics neurological disorders |
| title | Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders |
| title_full | Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders |
| title_fullStr | Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders |
| title_full_unstemmed | Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders |
| title_short | Influence of Metabolic, Transporter, and Pathogenic Genes on Pharmacogenetics and DNA Methylation in Neurological Disorders |
| title_sort | influence of metabolic transporter and pathogenic genes on pharmacogenetics and dna methylation in neurological disorders |
| topic | epigenetics DNA methylation pharmacogenetics neurological disorders |
| url | https://www.mdpi.com/2079-7737/12/9/1156 |
| work_keys_str_mv | AT olaiamartineziglesias influenceofmetabolictransporterandpathogenicgenesonpharmacogeneticsanddnamethylationinneurologicaldisorders AT vinogrannaidoo influenceofmetabolictransporterandpathogenicgenesonpharmacogeneticsanddnamethylationinneurologicaldisorders AT ivancarrera influenceofmetabolictransporterandpathogenicgenesonpharmacogeneticsanddnamethylationinneurologicaldisorders AT juancarloscarril influenceofmetabolictransporterandpathogenicgenesonpharmacogeneticsanddnamethylationinneurologicaldisorders AT nataliacacabelos influenceofmetabolictransporterandpathogenicgenesonpharmacogeneticsanddnamethylationinneurologicaldisorders AT ramoncacabelos influenceofmetabolictransporterandpathogenicgenesonpharmacogeneticsanddnamethylationinneurologicaldisorders |