Drug Development and Pharmacogenomics

A 32-year-old Indian woman with newly diagnosed hypertension is started on enalapril 10 mg daily. After 2 weeks, she develops severe angioedema of the lips and tongue requiring emergency management. Genetic testing reveals she carries a loss-of-function variant in the ACE gene (rs4646994 insertion/deletion polymorphism). Her brother, who also carries the same variant, tolerated enalapril well without angioedema. Which pharmacogenomic principle BEST explains the variable clinical response to enalapril in this family?

A 48-year-old Indian man with type 2 diabetes is started on metformin 500 mg twice daily. After 3 months of good glycemic control, he is switched to a newer agent, gliclazide, due to mild gastrointestinal side effects. One week later, he presents with severe hypoglycemia (blood glucose 42 mg/dL) requiring IV dextrose. His HbA1c is 6.8%. Genetic testing reveals he is a **CYP2C9 poor metabolizer** (homozygous *2/*2 allele). Which pharmacogenomic mechanism MOST directly explains his severe hypoglycemia with gliclazide?

Which of the following best describes the concept of pharmacogenomics in the context of drug development?