Why a saliva sample changes the right starting dose.
Pharmacogenomics is the part of medicine that says: the right drug at the right dose for one patient is the wrong drug at the wrong dose for the next, and the difference is sometimes a single base in a single gene. Here is the short version of the genes we screen for in GeneRx, and why each one shows up in the dosing algorithm.
CYP2D6 — Cytochrome P450 2D6
Metabolizes ~25% of all clinically used drugs. Activity ranges from poor metabolizer to ultra-rapid metabolizer based on copy number and SNP combinations.
*1 (normal), *2 (normal), *4 (no function), *10 (decreased), *17 (decreased), *xN (increased copies)
Determines starting dose and avoidance of certain co-prescribed antidepressants and opioids. Relevant when combining peptide therapy with SSRIs/SNRIs or pain medications.
CYP2C19 — Cytochrome P450 2C19
Metabolizes PPIs, clopidogrel, and several psychotropics. Phenotype distribution varies dramatically by ancestry.
*1 (normal), *2 (no function), *3 (no function), *17 (rapid)
PPI dose adjustments matter when peptide therapy causes reflux. Clopidogrel response gating is relevant for cardiovascular comorbidities.
MTHFR — Methylenetetrahydrofolate reductase
Converts 5,10-MTHF to 5-MTHF — the bioactive folate form needed for DNA methylation and homocysteine clearance.
C677T (677C>T → A222V), A1298C (1298A>C → E429A)
C677T homozygotes have ~30% reduced enzyme activity. Affects folate dosing decisions when supporting peptide therapy with B-vitamin protocols and informs cardiovascular risk stratification.
COMT — Catechol-O-methyltransferase
Degrades dopamine, norepinephrine, and epinephrine. Val158Met variant changes enzyme thermostability ~3–4×.
Val/Val (fast), Val/Met (intermediate), Met/Met (slow)
Met/Met patients can have higher prefrontal dopamine tone — relevant when interpreting energy and mood changes during GLP-1 induction. Also informs PT-141 response.
GLP1R — GLP-1 receptor
The actual binding target of all GLP-1 drugs. Coding variants change receptor surface expression and downstream cAMP signaling.
rs6923761 (Gly168Ser), rs10305420 (Pro7Leu)
rs6923761 G allele carriers have shown altered GLP-1 response in multiple trials — a meaningful signal when picking semaglutide vs tirzepatide and when planning the titration curve.
MC4R — Melanocortin-4 receptor
Critical satiety signaling node. Loss-of-function variants are the most common monogenic cause of obesity (~1–6% prevalence).
Multiple loss-of-function and gain-of-function variants
LoF carriers may need different dosing logic, and PT-141 (an MC4R agonist) response is heavily variant-dependent. Detection routes patients to setmelanotide-aware specialist care when warranted.
GIPR — Glucose-dependent insulinotropic polypeptide receptor
GIP arm of dual-agonist therapy (tirzepatide). Variants affect insulin secretion and adiposity signaling.
rs1800437 (Glu354Gln), rs10423928
Helps decide whether the GIP arm of a dual agonist is contributing — informs whether to escalate tirzepatide vs switch to GLP-1 mono.
CPIC = Clinical Pharmacogenetics Implementation Consortium. DPWG = Dutch Pharmacogenetics Working Group. Both publish dosing recommendations validated against clinical outcomes.
Variants flagged "Internal" are ones we use in our protocol but that have not yet reached a formal CPIC/DPWG dosing recommendation. We disclose the strength of evidence for each one in the GeneRx report itself.