Pharmacogenetic profile from the GnTech® TotalGene panel — four sub-modules (psychiatry / oncology / cardiology / infectious disease), with the patient's current medications cross-referenced against the gene–drug interaction tables.Perfil farmacogenético do painel GnTech® TotalGene — quatro submódulos (psiquiatria / oncologia / cardiologia / infectologia), com as medicações atuais do paciente cruzadas com as tabelas de interação gene-medicamento.
A tabela detalhada de interações farmacogenéticas e os módulos por especialidade ainda estão sendo traduzidos. Os títulos, descrições e a tabela de medicações atuais já estão bilíngues.
GnTech® TotalGene panel — buccal-cell sample collected 2023-05-28,
reported 2023-06-14. Four sub-modules: PsicoGene
(psychiatry / neurology), OncoGene, CardioGene,
InfectoGene. Method: Next-Generation Sequencing (NGS), Real-time PCR for CYP2D6 deletion/duplication, PCR electrophoresis for SLC6A4.
All clinical notes shown in English with (translated)
where the source is Portuguese.
Painel GnTech® TotalGene — amostra de células bucais coletada em 28/05/2023, laudo emitido em 14/06/2023. Quatro submódulos: PsicoGene (psiquiatria / neurologia, 91 medicações), OncoGene (oncologia), CardioGene (cardiologia) e FarmaGene (farmacologia geral). As interações gene-medicamento seguem as diretrizes CPIC / DPWG e são marcadas em verde / âmbar / vermelho.
Clinical summary (TL;DR for the treating team):
Duloxetine, diazepam and quetiapine (plus pregabalin, not on the PGx panel) sit in the GREEN “use as labelled” band: CYP2D6 *1/*1, CYP2C19 *1C/*1C, CYP3A4 *1/*1 normal metabolisers; FKBP5 A/A and SLC6A4 L/C predict favourable serotonergic response, supporting current SNRI choice. The newly-added Depakote ER (valproate) sits in AMBER — patient is CYP2C9 *1/*2 intermediate metaboliser and UGT2B15 reduced metaboliser, both relevant for valproate clearance; titrate cautiously.
MTHFR C677T + A1298C compound heterozygote with ~50% reduction in MTHFR enzyme activity — consider L-methylfolate adjunct to optimise antidepressant response; current B12 supplementation is appropriate but methylated folate is the actionable add-on.
Highest-stakes incidental finding: warfarin would require alternative agent or PGx-algorithm-guided dosing (CYP2C9 *1/*2 intermediate + VKORC1 increased sensitivity + CYP4F2 *3/*3); also avoid dabigatran (CES1 rs2244613 T/T elevated bleed risk), simvastatin (reduced response), and benazepril (reduced response). If anticoagulation ever needed, rivaroxaban is green.
CYP3A5 *3/*3 non-expresser — midazolam clearance is reduced (red flag); UGT2B15 reduced metaboliser — lorazepam and oxazepam can accumulate (relevant if benzodiazepine rotation is ever needed during the diazepam taper).
Other actionable incidental flags: phenytoin/fosphenytoin would need ~25% dose reduction (CYP2C9 intermediate); celecoxib/flurbiprofen start at lowest labelled dose; HLA-B *15:02 and HLA-A *31:01 negative — normal SJS/TEN risk for carbamazepine/oxcarbazepine; cisplatin would carry elevated ototoxicity risk (XPC G/T) if oncology ever relevant.
Patient's current medications & supplements vs PGx profile
Drug
Dose
Module
Genes
Risk band
Note (translated)
Depakote ER (divalproex)
750 mg/day new
PsicoGene
CYP2C9, UGT1A6, UGT2B15
Use with caution
Patient is CYP2C9 *1/*2 intermediate metaboliser and UGT2B15 reduced metaboliser — both contribute to valproate clearance. Start lower and titrate by clinical response & serum level. Hepatotoxicity, thrombocytopenia and ammonia screening recommended.
Lyrica (pregabalin)
225 mg/day · 2 tomadas ↑ from 150
PsicoGene
—
—
Drug is not listed in the PsicoGene panel. Pregabalin is predominantly renally excreted; the report has no gene–drug interaction data for this agent.
Quetiapine (Quetros)
50 mg/day to be reduced soon
PsicoGene
CYP3A4, MC4R
Use as labelled
Normal drug metabolism and lower risk of weight gain and hypertriglyceridaemia; standard precautions should be maintained. Evidence level: Moderate.
Cymbalta (duloxetine)
30 mg/day ↓ from 120
PsicoGene
CYP2D6
Use as labelled
Normal drug metabolism; standard precautions should be maintained. Evidence level: High. Monitor for SNRI-discontinuation symptoms after the large dose drop.
Valium (diazepam)
35 mg/day tapering
PsicoGene
CYP2C19, CYP3A4
Use as labelled
Normal drug metabolism; standard precautions should be maintained. Evidence level: High.
Vitamin B1 (Thiamine)
supplement
—
—
—
Outside the scope of this PGx panel.
Vitamin B12 (Cyanocobalamin)
supplement
—
MTHFR (indirectly)
—
Compound heterozygote MTHFR genotype with ~50% reduction in MTHFR enzyme activity. L-methylfolate supplementation may be appropriate; ongoing B12 use is reasonable, with consideration of methylated folate.
Vitamin D3
supplement
—
—
—
Outside the scope of this PGx panel.
Magnesium
supplement
—
—
—
Outside the scope of this PGx panel.
Melatonin
supplement
—
CYP1A2 (indirectly)
—
Not directly listed, but CYP1A2 *1M/*1M genotype implies inducible ultrarapid metabolism in smokers / heavy coffee consumers, which can lower exogenous melatonin exposure.
Browse the four modules
Psychiatry/neurology PGx panel covering 91 drugs across antidepressants, anxiolytics, mood stabilisers, antipsychotics, analgesics, opioid antagonists, cannabinoids, hypnotics, cholinesterase inhibitors, COMT inhibitors, monoamine transporter inhibitors, S1P modulators, non-stimulant CNS agents and psychostimulants. The patient is a normal metaboliser at all major hepatic CYP loci (CYP1A2 *1M/*1M, CYP2B6 *1/*4 rapid, CYP2C9 *1/*2 intermediate, CYP2C19 *1C/*1C, CYP2D6 *1/*1, CYP3A4 *1/*1) but a CYP3A5 non-expresser (*3/*3) and a UGT2B15 reduced metaboliser. A handful of drugs fall into amber (paroxetine, bupropion, selegiline, lorazepam, oxazepam, valproic acid, carbamazepine, phenytoin/fosphenytoin, phenobarbital, lithium, aripiprazole, iloperidone, celecoxib, fentanyl, flurbiprofen, methadone, naloxone, naltrexone, THC), and only midazolam is red because of the CYP3A5 non-expresser status.
Normal metaboliser (inducible ultrarapid in smokers / heavy CYP1A2 inducers)
CYP2B6
*1/*4
Rapid metaboliser
CYP2C9
*1/*2
Intermediate metaboliser
CYP2C9 (rs1057910)
A/A
Normal metaboliser
CYP2C19
*1C/*1C
Normal metaboliser
CYP2D6
*1/*1
Normal metaboliser
CYP3A4
*1/*1
Normal metaboliser
CYP3A5
*3/*3
Non-expresser (poor metaboliser) — most common phenotype in non-Africans
EPHX1 (rs1051740)
T/C
Elevated metaboliser
EPHX1 (rs2234922)
A/A
Reduced metaboliser
UGT1A4 (rs2011425)
T/T
Reduced metaboliser (lamotrigine)
UGT2B15 (rs1902023)
A/C
Reduced metaboliser (lorazepam, oxazepam)
MTHFR (rs1801131 c.1298A>C)
A/C
Heterozygous
MTHFR (rs1801133 c.677C>T)
C/T
Heterozygous; combined ~50% reduction in MTHFR enzyme activity
Response & toxicity genes
ABCB1 (rs1045642)
G/G
Reduced response
ABCB1 (rs2032583)
A/A
Reduced risk of adverse effects
ADRA2A (rs1800544)
G/C
Favourable response
ANKK1 (rs1800497)
G/G
Drug-dependent toxicity/response
BDNF (rs962369)
T/T
Reduced risk of adverse effects
BDNF (rs61888800)
G/G
Favourable response
COMT (rs4680)
G/A
Drug-dependent response
COMT (rs13306278)
C/C
Favourable response
CYP3A4 (rs2242480)
C/C
Reduced response
DRD1 (rs4532)
C/T
Reduced risk of adverse effects
DRD2 (rs1799978)
T/T
Favourable response
FKBP5 (rs4713916)
A/A
Favourable response (antidepressants)
G6PD
B/-
Normal G6PD activity
GRIK4 (rs1954787)
T/C
Reduced response
GSK3B (rs334558)
A/G
Favourable response
GSK3B (rs6438552)
A/G
Reduced response
HLA-A (rs1061235)
WT/WT
HLA-A *31:01 negative (normal SJS/TEN risk with carbamazepine)
HLA-B (rs144012689)
WT/WT
HLA-B *15:02 negative (normal SJS/TEN risk with carbamazepine, oxcarbazepine, phenytoin)
HTR1A (rs6295)
C/G
Reduced response
HTR2A (rs7997012)
G/G
Reduced response
HTR2C (rs1414334)
G/-
Reduced risk of adverse effects (weight gain)
HTR2C (rs3813929)
C/-
Elevated risk of adverse effects
MC4R (rs489693)
C/A
Reduced risk of adverse effects (weight gain) with antipsychotics
OPRD1 (rs678849)
T/T
Favourable response (opioids)
OPRM1 (rs1799971)
A/A
Drug-dependent toxicity/response (opioids)
SLC6A2 (rs28386840)
T/A
Favourable response
SLC6A4 (5-HTTLPR)
L/C
Favourable response (SSRIs)
rs2952768
T/T
Favourable response (opioid analgesics)
Key recommendations
All major CYPs (1A2, 2C19, 2D6, 3A4) are normal metabolisers — standard dosing of duloxetine, quetiapine, diazepam should be expected to behave normally.
CYP3A5 *3/*3 non-expresser — midazolam clearance reduced (red flag in PsicoGene module).
UGT2B15 reduced metaboliser — lorazepam/oxazepam plasma levels can be elevated; consider dose reduction (amber).
CYP2C9 *1/*2 intermediate — phenytoin / fosphenytoin require ~25% maintenance dose reduction per CPIC; celecoxib and flurbiprofen should be started at the lowest labelled dose.
HLA-B *15:02 and HLA-A *31:01 negative — normal SJS/TEN risk with carbamazepine, oxcarbazepine, phenytoin.
MTHFR compound heterozygote with ~50% reduced enzyme activity — L-methylfolate supplementation may improve antidepressant response.
FKBP5 A/A and SLC6A4 L/C — favourable serotonergic response markers (relevant for duloxetine, escitalopram, fluoxetine, sertraline, paroxetine, venlafaxine).
Paroxetine is amber due to conflicting FKBP5/HTR1A response signals — prefer duloxetine, escitalopram, sertraline if SSRI/SNRI rotation is being considered.
Bupropion and selegiline (both CYP2B6 substrates) may require dose increase due to rapid CYP2B6 metaboliser status.
Oncology PGx panel of 26 agents (analgesics, antiemetics, antineoplastics, immunosuppressants, hyperuricaemia prophylactics). Patient has normal DPYD, NUDT15, TPMT and UGT1A1 metabolism, normal G6PD activity, but is CYP2C9 *1/*2 intermediate metaboliser and CYP3A5 *3/*3 non-expresser. Only one drug is amber: cisplatin (XPC G/T heterozygote = elevated risk of cisplatin-induced ototoxicity and neutropenia). All other oncology agents are green for this patient.
Tamoxifen: CYP2D6 *1/*1 yields therapeutic endoxifen — avoid strong/moderate CYP2D6 inhibitors but standard dose 20 mg/day expected to work.
Tacrolimus: CYP3A5 *3/*3 non-expresser — standard starting dose with therapeutic drug monitoring.
Fluoropyrimidines (5-FU, capecitabine, tegafur): normal DPD activity — standard dosing.
Thiopurines (azathioprine, mercaptopurine, thioguanine): normal TPMT and NUDT15 — normal myelosuppression risk.
Cardiology PGx panel of ~30 agents across ARBs, antianginals, antiarrhythmics, antithrombotics/anticoagulants, PPAR activators, beta-blockers, calcium-channel blockers, diuretics, statins and ACE inhibitors. The Warfarin response sub-analysis shows CYP2C9 *1/*2 intermediate + VKORC1 *1/*2 increased sensitivity + CYP4F2 *3/*3 carrier — the report flags: “Consider an alternative agent. If not possible, calculate the dose using a published, validated pharmacogenetic algorithm (e.g. warfarindosing.org), and increase the calculated dose by 5–10% to account for the CYP4F2 carrier status when not included in the algorithm.” Most cardiac drugs are green; amber-flag drugs include irbesartan, losartan, acenocoumarol, clopidogrel, phenprocoumon, bumetanide, furosemide, torsemide, pravastatin. Red-flag drugs include simvastatin, benazepril, dabigatran.
Drug classes
Angiotensin II receptor antagonists (Antagonistas dos Receptores de Angiotensina II)
Calcium-channel blockers (Bloqueadores de canais de cálcio)
Use as labelled
Amlodipine
Diuretics (Diuréticos)
Use as labelled
Hydrochlorothiazide
Use with attention
BumetanideFurosemideTorsemide
Statins (Estatinas)
Use as labelled
AtorvastatinLovastatinPitavastatinRosuvastatin
Use with attention
Pravastatin
Use with caution
Simvastatin
ACE inhibitors (Inibidores da Enzima Conversora de ECA)
Use as labelled
CaptoprilPerindoprilQuinapril
Use with caution
Benazepril
Warfarin dosing.
Consider an alternative anticoagulant. If warfarin is required, calculate the starting dose using a published, validated PGx algorithm (e.g. GAGE / warfarindosing.org). For non-African-descent patients, increase the calculated dose by 5–10% if the algorithm does not include CYP4F2.
Metabolism genes
CES1 (rs2244613)
T/T
Reduced metaboliser — elevated dabigatran bleeding risk in atrial fibrillation
CES1 (rs8192935)
G/G
Elevated metaboliser — may reduce dabigatran plasma concentration
CES1 (rs71647871)
C/C
Elevated metaboliser
CYP2C (rs12777823)
G/G
Non-carrier of rs12777823 A (warfarin)
CYP2C9
*1/*2
Intermediate metaboliser
CYP2C19
*1C/*1C
Normal metaboliser
CYP2D6
*1/*1
Normal metaboliser
CYP3A4
*1/*1
Normal metaboliser
CYP4F2 (rs2108622)
*3/*3
Homozygous carrier of rs2108622 T allele — warfarin dose increase 5–10%
SLCO1B1
*1/*1
Normal hepatic statin transport
Response & toxicity genes
ABCB1 (rs1045642)
G/G
Elevated metaboliser (digoxin)
ABCB1 (rs2032582)
C/C
Drug-dependent metabolism/response (reduced response to simvastatin)
ABCG2 (rs2231142)
G/G
Normal metaboliser
ACE (rs1799752)
WT(DEL)/Ins
Favourable response to captopril/quinapril
ADRB2 (rs1042714)
C/C
Reduced risk of atenolol-induced hypertriglyceridaemia
AGT (rs5051)
C/T
Reduced response (benazepril)
AGT (rs7079)
T/T
Favourable response (benazepril)
AGTR1 (rs275651)
T/T
Favourable response (perindopril)
APOA5 (rs662799)
A/A
Favourable LDL response to atorvastatin / lovastatin / simvastatin
APOA5 (rs3135506)
G/C
Favourable triglyceride/HDL response to fenofibrate
Losartan/irbesartan: CYP2C9 intermediate — slower clearance, larger antihypertensive effect possible (no formal dose adjustment).
F5 (Factor V Leiden) absent — no inherited thrombophilia from this variant.
Infectious-disease PGx panel: antibiotics, antifungals, antiparasitics, antivirals, appetite stimulants. Patient has normal G6PD (so anti-malarials, sulfas, dapsone, primaquine, tafenoquine, nitrofurantoin, fluoroquinolones are all green for haemolytic-anaemia risk), normal CYP2C19 (voriconazole green), CYP2B6 *1/*4 rapid metaboliser (efavirenz: slightly lower plasma levels but standard 600 mg/day suggested), and UGT1A1 *1/*1 normal. Two amber flags: atazanavir (CYP2C19 + UGT1A1 interaction with ritonavir/voriconazole co-prescription) and nevirapine (ABCB1 G/G — elevated hepatotoxicity risk). No red flags.