Pharmacogenomics

Major enzyme for metabolizing ~25% of medications including opioids, antidepressants, and beta-blockers

Decreased function CYP2D6 variant common in Asian populations

No-function CYP2C19 variant affecting PPIs, clopidogrel, and some antidepressants

Increased function CYP2C19 variant - rapid/ultrarapid metabolizer

Decreased function variant affecting warfarin, phenytoin, and NSAIDs

No-function CYP2C9 variant with major warfarin implications

Caffeine metabolism - affects how quickly you process caffeine

Statin transport - affects muscle side effect risk with statins

Warfarin sensitivity - determines initial dosing

Factor V Leiden - blood clotting disorder affecting thrombosis risk

Alcohol metabolism - flush reaction and cancer risk

Common CYP2D6 variant defining the *2 allele; previously considered normal-function but recent evidence shows reduced expression through altered splicing

Frameshift deletion causing no enzyme function, defining poor metabolizer status for many drugs including codeine, tramadol, and antidepressants

Intronic splice variant causing decreased CYP2D6 enzyme activity through aberrant splicing

Splice site variant creating a non-functional CYP3A5 enzyme, dramatically affecting metabolism of tacrolimus and other immunosuppressants

Decreased-function variant affecting metabolism of efavirenz, methadone, bupropion, and cyclophosphamide

Most critical pharmacogenomic variant causing complete loss of DPD enzyme function; increases fatal 5-FU/capecitabine toxicity risk 25-fold without dose reduction

Decreased-function variant reducing DPD enzyme activity ~30%, requiring 50% fluoropyrimidine dose reduction

No-function variant causing deficient thiopurine methylation; most common TPMT deficiency allele in East Asian and African populations

Reduces ABCG2 transporter function affecting rosuvastatin levels and uric acid excretion, increasing risk for statin side effects and gout

Reduces vitamin K metabolism, requiring higher warfarin doses to achieve anticoagulation

Mu-opioid receptor variant affecting opioid response, pain sensitivity, and potentially naltrexone efficacy

Synonymous variant in P-glycoprotein affecting drug efflux pump expression and hundreds of substrate drugs

Phase II glucuronidation enzyme that metabolizes bilirubin and many drugs including irinotecan; reduced activity causes Gilbert syndrome and severe chemotherapy toxicity

Promoter variant affecting CYP3A4 expression, most common in African populations

Nucleotide diphosphatase that inactivates toxic thiopurine metabolites; reduced function causes severe myelosuppression at standard drug doses

GLP-1 receptor variant that alters response to GLP-1 agonist medications used for weight loss and type 2 diabetes

Missense variant in the GLP-1 receptor that alters drug response to GLP-1 agonists (Ozempic, Wegovy, Saxenda) and DPP-4 inhibitors, with genome-wide significant protection against type 2 diabetes in East Asians

Rare protective missense variant in the GLP-1 receptor associated with lower fasting glucose, reduced T2D risk, and coronary heart disease protection

GLP-1 receptor variant in intracellular loop 2 that alters receptor surface expression and signaling, influencing antipsychotic response, cortisol regulation, and bone metabolism

Intronic splice variant causing ~50% reduced CYP3A4 mRNA expression, affecting metabolism of ~50% of all prescription drugs

Intronic variant in the OCT1 organic cation transporter reducing hepatic metformin uptake and altering response to multiple cation-transported drugs