Core49: Pharmacogenetics, pharmacogenomics - definition, examples

🧬 High-yield / 要点：Pharmacogenetics focuses on genetic variation affecting drug metabolism; pharmacogenomics broadly includes genetic variation affecting drug effects and side effects.

Definitions / 定義

• Pharmacogenetics:
  • Primarily refers to genetic variations in drug metabolism.
• Pharmacogenomics:
  • Broader term for genetic variations responsible for drug effects and adverse effects.
• In practice, the terms are often used similarly.

Purpose / 目的

• Uses human genetic polymorphisms to explain:
  • Different drug responses.
  • Different side-effect risk.
  • Different dose requirements.
  • Treatment failure in some patients.

Example: clopidogrel / 例：クロピドグレル

• Clopidogrel requires metabolic activation.
• CYP2C19 encodes an enzyme involved in clopidogrel metabolism.
• Genetic variants can reduce activation and lower antiplatelet effect.
• Patients with reduced-function CYP2C19 alleles have higher cardiovascular event risk compared with normal metabolizers.

Other genetic factors / その他の遺伝要因

• ABCB1 variants can also influence clopidogrel response.
• Example from lecture:
  • ABCB1 3435 TT genotype associated with higher cardiovascular event rate compared with wild type.

Clinical meaning / 臨床的意義

• Genotyping can help predict:
  • Non-response.
  • Toxicity risk.
  • Need for alternative therapy.
• Especially important when the drug has:
  • Narrow therapeutic index.
  • Serious consequences of treatment failure.
  • Strong dependence on metabolic activation/inactivation.

Remember / 覚え方

• Gene variant → metabolism/effect changes
• CYP2C19 loss-of-function → clopidogrel less effective
• Pharmacogenomics supports individualized medicine