Pharmacogenetics of CYP2A6, CYP2B6, and UGT2B7 in the Context of HIV Treatments in African Populations
Abstract
:1. Introduction
1.1. Known Variants
1.1.1. CYP2A6
1.1.2. CYP2B6
1.1.3. CYP3A4
1.1.4. UGT2B7
1.2. Treatment and Dosage Guidelines
2. Materials and Methods
2.1. Data and Ethics
2.2. Analysis and Pipeline Development
Data Preparation
3. Analysis
4. Results
4.1. Variant and Population Partitions Characterisation
4.2. Fisher’s Exact Test
4.3. Variant Effect Prediction
4.3.1. Variants with Known Phenotype Associations
4.3.2. Novel Variants and Their Potential Pathogenicity
5. Discussion
5.1. Variant Frequency
5.2. Variant Impact
6. Conclusions
Limitations of the Study
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Start Coordinates (Source—100 bp) | Stop Coordinates (Source +100 bp) | Region Size |
---|---|---|---|
CYP2A6 | 41,349,343 bp (e! and UCSC) | 41,356,460 bp (NCBI) | 7117 bp |
CYP2B6 | 41,497,104 bp (e! and UCSC) | 41,524,408 bp (NCBI) | 27,304 bp |
UGT2B7 | 69,916,981 bp (e!) | 69,978,805 bp (All) | 61,624 bp |
Gene | Variants Identified | Alleles (1% or More) | Two-Tailed Significance ( = 0.05) |
---|---|---|---|
CYP2A6 | 413 | 103 | 159 |
CYP2B6 | 1586 | 322 | 771 |
UGT2B7 | 2469 | 736 | 957 |
rsID | Haplotypes(pheno.) | AFR vs. other | AMR vs. AFR | EUR vs. AFR | EAS vs. AFR | SAS vs. AFR |
---|---|---|---|---|---|---|
rs6413474 | *1, *1×2↑, *21† | 0% ↓ | 0.58% ↑ | 1.19% ↑ | - | 0.82% ↑ |
rs28399463 | *1, *1×2↑, *28†, *44† | 2.65% ↑ | 0.29% ↓ | 0% ↓ | 0% ↓ | 0.1% ↓ |
rs1809810 | *1, *1× 2↑, *18†, *19† | 0.61% ↓ | 1.59% ↑ | 1.59% ↑ | - | 2.25% ↑ |
rs28399454 | *1, *1× 2↑, *17↓ | 11.9% ↑ | 0.58% ↓ | 0% ↓ | 0.1% ↓ | 0% ↓ |
rs56256500 | *1, *1× 2↑, *16†, *23† | 1.97% ↑ | 0% ↓ | 0% ↓ | 0% ↓ | 0% ↓ |
rs199916117 | - | 0% ↓ | - | - | 1.49% ↑ | - |
rs1801272 | *1, *1×2↑, *2↓ | 0.08% ↓ | 0.72% ↑ | 3.38% ↑ | - | 0.61% ↑ |
rs28399440 | *1, *1×2↑, *9↓, *13†, *15†, *50† | 1.81% ↑ | 0% ↓ | 0% ↓ | 0% ↓ | 0% ↓ |
rs72549435 | *1, *1× 2↑, *24†, *49† | 1.06% ↑ | 0.14% ↓ | 0% ↓ | 0.1% ↓ | 0% ↓ |
rs145308399 | - | 0.15% ↕ | 0% ↓ | - | - | 2.15% ↑ |
rs28399435 | *1, *1×2↑, *14† | 0.38% ↓ | 1.73% ↑ | 3.28% ↑ | - | 2.25% ↑ |
rs72549432 | *1, *1× 2↑, *31† | 1.13% ↑ | 0% ↓ | 0% ↓ | 0% ↓ | 0% ↓ |
rs34883432 | *1, *10‡ | 0% ↓ | 1.3% ↑ | 0.7% ↑ | - | - |
rs8192709 | *1, *2, *10‡ | 4.3% ↑ | 0.29% ↓ | 6.26% ↓ | - | - |
rs33980385 | *1, *17 | 1.29% ↑ | - | 0% ↓ | 0% ↓ | 0% ↓ |
rs33926104 | *1, *17 | 1.29% ↑ | 0.29% ↓ | 0% ↓ | 0% ↓ | 0% ↓ |
rs34284776 | *1, *17 | 1.29% ↑ | 0.29% ↓ | 0% ↓ | 0% ↓ | 0% ↓ |
rs3745274 | *1, *6↓, *7↓, *9↓, *13⊘, *19↓, *20↓, *26↓, *34↓, *36↓, *37⊘, *38⊘ | 37.95% ↑ | - | 23.56% ↓ | 21.53% ↓ | - |
rs139029625 | *1, *35⊘ | 1.21% ↑ | 0% ↓ | 0% ↓ | 0% ↓ | 0% ↓ |
rs28399499 | *1, *18⊘ | 8.56% ↑ | 1.01% ↓ | 0% ↓ | 0% ↓ | 0% ↓ |
rs3211371 | *1, *5, *7↓, *33‡, *34↓ | 1.21% ↕ | 7.21% ↑ | 11.23% ↑ | 0.3% ↓ | 8.9% ↑ |
rs12233719 | - | 0.08% ↓ | - | - | 13.19% ↑ | 0.72% ↑ |
rs7439366 | - | 77.49% ↑ | 68.01 ↓ | 51.49% ↓ | 72.52% ↓ | 60.12% ↓ |
Gene | Position | Reference | Alternate | Consequence |
---|---|---|---|---|
CYP2A6 | 40843668 | T | C | 3’ UTR variant |
CYP2A6 | 40848968 | G | GA | Intron variant |
CYP2B6 | 40992518 | T | C | Intron variant |
CYP2B6 | 40995794 | ATGATATT | A | Intron variant |
CYP2B6 | 40996689 | T | C | Intron variant |
CYP2B6 | 41001709 | G | A | Intron variant |
CYP2B6 | 41008210 | T | TTTG | Intron variant |
CYP2B6 | 41017322 | C | A | 3’ UTR variant |
UGT2B7 | 69046035 | T | A | Downstream gene variant |
UGT2B7 | 69052469 | G | GT | Mapping Failure * |
UGT2B7 | 69053111 | A | G | Intron variant |
UGT2B7 | 69056859 | T | C | Intron variant |
UGT2B7 | 69058254 | C | T | Intron variant |
UGT2B7 | 69059862 | C | G | Intron variant |
UGT2B7 | 69060704 | G | C | Intron variant |
UGT2B7 | 69063327 | A | AAAAAAGG | Intron variant |
UGT2B7 | 69063329 | A | AAAAGAAAG | Intron variant |
UGT2B7 | 69064070 | A | AAG | Intron variant |
UGT2B7 | 69064096 | G | GAA | Intron variant |
UGT2B7 | 69070106 | G | C | Intron variant |
UGT2B7 | 69078334 | C | T | Intron variant |
UGT2B7 | 69092102 | A | AT | Mapping Failure * |
UGT2B7 | 69099275 | AAAAG | A | Intron variant |
UGT2B7 | 69100656 | G | A | Intron variant |
UGT2B7 | 69104655 | G | A | Intron variant |
UGT2B7 | 69107691 | T | C | Intron variant |
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Ford, G.R.; Niehaus, A.; Joubert, F.; Pepper, M.S. Pharmacogenetics of CYP2A6, CYP2B6, and UGT2B7 in the Context of HIV Treatments in African Populations. J. Pers. Med. 2022, 12, 2013. https://doi.org/10.3390/jpm12122013
Ford GR, Niehaus A, Joubert F, Pepper MS. Pharmacogenetics of CYP2A6, CYP2B6, and UGT2B7 in the Context of HIV Treatments in African Populations. Journal of Personalized Medicine. 2022; 12(12):2013. https://doi.org/10.3390/jpm12122013
Chicago/Turabian StyleFord, Graeme R., Antoinette Niehaus, Fourie Joubert, and Michael S. Pepper. 2022. "Pharmacogenetics of CYP2A6, CYP2B6, and UGT2B7 in the Context of HIV Treatments in African Populations" Journal of Personalized Medicine 12, no. 12: 2013. https://doi.org/10.3390/jpm12122013