The Case for Pre-Emptive Pharmacogenetic Screening in South Africa
Abstract
:1. Introduction
2. Materials and Methods
2.1. Processing and Analysis of Hospital Dispensary Files
2.2. Extraction of Allele Frequency Data
2.3. Analysis of the South African Health Products Regulatory Authority VigiLyze Dataset
3. Results
3.1. Comparison of PREPARE Study Drugs with Steve Biko Academic Hospital Dispensary Data
3.2. Population-Based Allele Frequency Comparisons
3.3. Analysis of the South African Health Products Regulatory Authority VigiLyze Dataset
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Pharmacy | Year | Prescription Number | Cumulative Prescriptions | Total Cost (ZAR) | Cumulative Cost (ZAR) |
---|---|---|---|---|---|
Inpatient | 2018 | 477,254 | 1,751,386 | 28,900,337.69 | 117,892,639.02 |
2019 | 459,999 | 30,319,287.36 | |||
2020 | 453,137 | 31,785,757.32 | |||
2021 | 360,996 | 26,887,256.65 | |||
Outpatient | 2018 | 1,169,679 | 4,288,797 | 43,350,476.40 | 186,686,832.97 |
2019 | 1,106,479 | 45,458,498.01 | |||
2020 | 1,103,182 | 52,555,138.32 | |||
2021 | 909,457 | 45,322,720.24 | |||
Oncology | 2018 | 205,341 | 758,697 | 18,034,013.16 | 64,540,893.00 |
2019 | 207,669 | 13,907,246.91 | |||
2020 | 198,983 | 24,021,552.54 | |||
2021 | 146,704 | 8,578,080.39 | |||
Total | 2018–2021 | 6,798,880 | 369,120,364.99 |
Drug Class | Prescription Number | Total Cost (ZAR) | Genes Monitored | dbSNPs Monitored |
---|---|---|---|---|
Analgesic | 217,572 | 5,848,133.71 | CYP2D6 | 13 |
Cholesterol-lowering | 207,018 | 3,444,997.81 | SLCO1B1 | 3 |
Antidepressant (TCA) | 109,345 | 684,720.60 | CYP2D6/CYP2C19 | 23 |
Antiepileptic | 38,216 | 1,834,534.52 | HLA B*5701/CYP2C19 | 6 |
Anticancer | 37,801 | 7,648,288.64 | DPYD/UGT1A1/CYP2D6 | 20 |
Anticoagulation | 21,370 | 1,642,319.46 | CYP2C9/CYP2C19/VKOR1 | 11 |
Anti-infective | 21,357 | 553,183.30 | CYP2B6/HLA B*5701/CYP2C9 | 14 |
Antidepressant | 20,180 | 476,304.87 | CYP2D6/CYP2C19 | 23 |
Immunosuppressive | 18,123 | 10,206,762.30 | TPMT/CYP3A5 | 6 |
Antipsychotic | 4274 | 762,684.76 | CYP2D6/CYP1A2 | 15 |
Total | 695,256 | 33,101,929.97 |
Drug Class | Description | Total Number of Prescriptions Issued | Cost (ZAR) |
---|---|---|---|
Analgesic | Tramadol | 217,546 | 5,836,578.7 |
Cholesterol-lowering | Simvastatin | 142,450 | 1,205,186.0 |
Antidepressant (TCA) | Amitriptyline | 109,340 | 684,461.7 |
Cholesterol-lowering | Atorvastatin | 64,568 | 2,239,811.8 |
Antipileptic | Carbamazepine | 29,287 | 1,307,022.6 |
Anticancer | Tamoxifen | 20,048 | 765,132.7 |
Anti-infective | Flucloxacillin | 17,754 | 241,172.0 |
Antidepressant | Citalopram | 15,969 | 176,589.1 |
Anticoagulant | Clopidogrel | 11 157 | 910,518.3 |
Anticancer | Fluorouracil | 10,971 | 281,973.2 |
Anticoagulant | Warfarin | 10,213 | 731,801.2 |
Immunosuppressive | Tacrolimus | 10,156 | 9,413,587.5 |
Antiepileptic | Phenytoin | 8929 | 527,511.9 |
Immunosuppressive | Azathioprine | 7967 | 793,174.8 |
Anticancer | Capecitabine | 4238 | 4,386,219.7 |
Anti-infective | Efavirenz | 3565 | 174,476.0 |
Antipsychotic | Haloperidol | 2965 | 88,551.0 |
Antidepressant | Sertraline | 2108 | 156,890.4 |
Antidepressant | Venlafaxine | 2059 | 138,826.1 |
Immunosuppressive | Mercaptopurine | 1508 | 1,600,266.0 |
Antipsychotic | Aripiprazole | 1032 | 648,508.4 |
Anticancer | Irinotecan | 857 | 213,280.9 |
Antipsychotic | Clozapine | 247 | 23,949.7 |
Immunosuppressive | Thioguanine | 179 | 401,416.1 |
Antidepressant | Paroxetine | 44 | 3999.3 |
Anti-infective | Voriconazole | 38 | 137,535.3 |
Antipsychotic | Zuclopenthixol | 30 | 1675.7 |
Analgesic | Codeine | 26 | 11,555.0 |
Antidepressant (TCA) | Imipramine | 5 | 258.9 |
Genes | Allele | dbSNP rsID Number | Functional Status | Allele Frequency European | Allele Frequency Sub-Saharan Africa | Fold Enrichment |
---|---|---|---|---|---|---|
CYP3A5 | *6 | rs10264272 | No function | 0.00151 | 0.19324 | 127.6 |
CYP2D6 | *29 | rs61736512/ rs59421388 | Decreased function | 0.00105 | 0.10833 | 103.5 |
CYP2C9 | *5 | rs28371686 | Decreased function | 0.00017 | 0.01033 | 59.2 |
UGT1A1 | *37 | rs8175347 | Decreased function | 0.00069 | 0.03707 | 54.0 |
CYP2D6 | *17 | rs28371706 | Decreased function | 0.00392 | 0.19355 | 49.4 |
CYP2C9 | *8 | rs7900194 | Decreased function | 0.00181 | 0.07585 | 42.0 |
CYP2C19 | *9 | rs17884712 | Decreased function | 0.00066 | 0.02696 | 40.8 |
CYP1A2 ^ | *1C | rs2069514 | Decreased function | 0.01298 | 0.27690 | 21.3 |
CYP2C9 | *11 | rs28371685 | Decreased function | 0.00164 | 0.02569 | 15.6 |
TPMT | *3C | rs1142345 | No function | 0.00492 | 0.05288 | 10.7 |
UGT1A1 ^ | *27 | rs35350960 | Decreased function | 0.00001 | 0.00004 | 5.2 |
CYP2D6 | *10 | rs1065852 | Decreased function | 0.01571 | 0.04869 | 3.1 |
CYP2D6 | *5 | Deletion | No function | 0.02948 | 0.06209 | 2.1 |
CYP2C19 | *3 | rs4986893 | No function | 0.00162 | 0.00267 | 1.6 |
CYP2B6 | *6 | rs3745274 | Decreased function | 0.23298 | 0.37487 | 1.6 |
UGT1A1 | *28 | rs8175347 | Decreased function | 0.31647 | 0.40004 | 1.3 |
CYP2C19 | *2 | rs4244285 | No function | 0.14686 | 0.15684 | 1.1 |
CYP1A2 ^ | *1F | rs762551 | Increased function | 0.71180 | 0.60500 | 0.8 |
CYP2C19 | *17 | rs12248560 | Increased function | 0.21544 | 0.17334 | 0.8 |
CYP2D6 | *41 | rs28371725 | Decreased function | 0.09238 | 0.04529 | 0.5 |
VKORC1 | X | rs9934438 | Decreased function | 0.41326 | 0.10774 | 0.3 |
CYP3A5 | *3 | rs776746 | No function | 0.92438 | 0.24095 | 0.3 |
SLCO1B1 | *15 | rs4149056 | No function | 0.15017 | 0.02793 | 0.2 |
HLA-B*5701 | X | rs2395029 | 0.03604 | 0.00609 | 0.2 | |
CYP2D6 | *4 | rs3892097 | No function | 0.18485 | 0.02873 | 0.2 |
CYP2C9 | *3 | rs1057910(C) | No function | 0.07554 | 0.01116 | 0.1 |
CYP2C9 | *2 | rs1799853 | Decreased function | 0.12730 | 0.01311 | 0.1 |
CYP3A5 | *7 | rs41303343 | No function | 0.00000 | 0.08641 | n/a |
CYP2D6 | *3 | rs35742686 | No function | 0.01592 | 0.00098 | n/a |
CYP2B6 | *18 | rs28399499 | No function | 0.00000 | 0.05768 | n/a |
CYP2C19 | *4A/B | rs28399504 | No function | 0.00236 | 0.00000 | n/a |
CYP2C19 | *5 | rs56337013 | No function | 0.00003 | 0.00000 | n/a |
CYP2C19 | *6 | rs72552267 | No function | 0.00030 | 0.00000 | n/a |
CYP2C19 | *7 | rs72558186 | No function | 0.00000 | 0.00000 | n/a |
CYP2C19 | *8 | rs41291556 | No function | 0.00336 | 0.00000 | n/a |
CYP2C19 | *10 | rs6413438 | Decreased function | 0.00000 | 0.00000 | n/a |
CYP2D6 | *6 | rs5030655 | No function | 0.01120 | 0.00000 | n/a |
CYP2D6 | *8 | rs5030865 | No function | 0.00022 | 0.00000 | n/a |
CYP2D6 | *9 | rs5030656 | Decreased function | 0.02754 | 0.00000 | n/a |
CYP2D6 | *14A/B | rs5030865 | Decreased function | 0.00000 | 0.00000 | n/a |
DPYD | *2A | rs3918290 | No function | 0.00792 | 0.00000 | n/a |
DPYD | *13 | rs55886062 | No function | 0.00056 | 0.00000 | n/a |
DPYD | c.2846 A>T | rs67376798 | Decreased function | 0.00374 | 0.00000 | n/a |
DPYD | c.1236G>A | rs56038477 | Decreased function | 0.02374 | 0.00000 | n/a |
SLCO1B1 | *5 | rs4149056 | No function | 0.02040 | 0.00000 | n/a |
TPMT | *2 | rs1800462 | No function | 0.00206 | 0.00000 | n/a |
TPMT | *3B | rs1800460 | No function | 0.00283 | 0.00000 | n/a |
UGT1A1 | *6 | rs4148323 | Decreased function | 0.00787 | 0.00000 | n/a |
Drug Class | Drug | Concomitant | Interacting | Suspected |
---|---|---|---|---|
Anti-infective | Efavirenz FDC | 71 | 1 | 522 |
Anti-infective | Efavirenz | 179 | 1 | 384 |
Cholesterol-lowering | Atorvastatin | 260 | 285 | |
Anticoagulant | Warfarin | 78 | 1 | 178 |
Cholesterol-lowering | Simvastatin | 313 | 136 | |
Antidepressant | Citalopram | 62 | 125 | |
Antidepressant (TCA) | Amitriptyline | 89 | 95 | |
Analgesic | Tramadol | 59 | 84 | |
Antiepileptic | Carbamazepine | 36 | 64 | |
Antipsychotic | Clozapine | 4 | 59 | |
Antipsychotic | Haloperidol | 15 | 48 | |
Anticoagulant | Clopidogrel | 52 | 36 | |
Antiepileptic | Phenytoin | 14 | 36 | |
Antidepressant | Sertraline | 26 | 24 | |
Antipsychotic | Zuclopenthixol | 14 | 22 | |
Immunosuppressive | Tacrolimus | 9 | 21 | |
Anticancer | Capecitabine | 3 | 18 | |
Anti-infective | Voriconazole | 0 | 17 | |
Immunosuppressive | Azathioprine | 16 | 13 | |
Antipsychotic | Aripiprazole | 5 | 11 | |
Analgesic | Codeine | 15 | 6 | |
Anticancer | Tamoxifen | 1 | 5 | |
Anti-infective | Flucloxacillin | 1 | 4 | |
Anticancer | Irinotecan | 1 | 3 | |
Antidepressant | Paroxetine | 8 | 3 | |
Anticancer | Fluorouracil | 2 | 2 | |
Antidepressant (TCA) | Imipramine | 1 | 1 | |
Antidepressant | Venlafaxine | 20 | 4 | 0 |
Total | 1354 | 7 | 2202 |
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Hurrell, T.; Naidoo, J.; Masimirembwa, C.; Scholefield, J. The Case for Pre-Emptive Pharmacogenetic Screening in South Africa. J. Pers. Med. 2024, 14, 114. https://doi.org/10.3390/jpm14010114
Hurrell T, Naidoo J, Masimirembwa C, Scholefield J. The Case for Pre-Emptive Pharmacogenetic Screening in South Africa. Journal of Personalized Medicine. 2024; 14(1):114. https://doi.org/10.3390/jpm14010114
Chicago/Turabian StyleHurrell, Tracey, Jerolen Naidoo, Collen Masimirembwa, and Janine Scholefield. 2024. "The Case for Pre-Emptive Pharmacogenetic Screening in South Africa" Journal of Personalized Medicine 14, no. 1: 114. https://doi.org/10.3390/jpm14010114