Pharmacogenomics

Pharmacogenetics and Pharmacogenomics

• Pharmacogenetics primarily focuses on how an individual's genetic makeup affects their response to drugs.
• Pharmacogenomics concerns the broader study of how all of a person’s genes (genome) may affect responses to medications.

Genotype to Phenotype Approach

• The genotype to phenotype approach is vital for understanding the relationship between genetic variations (genotype) and observable traits or drug responses (phenotype).

Variability in Drug Response

• A significant factor contributing to variability in drug response among individuals is genetic polymorphism, which impacts drug metabolism and efficacy.

PGxOne Test

• The PGxOne test provides insights into genetic variants that affect drug metabolism and can help predict individual responses to medications.

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

• The primary cause of G6PD deficiency is a mutation in the G6PD gene, leading to reduced enzyme activity in red blood cells.
• Males, particularly those of African, Mediterranean, or Asian descent, are more commonly affected by G6PD deficiency.

Medications to Avoid with G6PD Deficiency

• Individuals with G6PD deficiency should avoid medications such as sulfa drugs, certain antibiotics, and antimalarials, as they may increase the risk of hemolytic anemia.

Single Nucleotide Polymorphisms (SNPs)

• SNPs are variations in a single nucleotide in the DNA sequence among individuals, which can influence drug metabolism and response.

VKORC1 and Warfarin Sensitivity

• The VKORC1 variant is associated with sensitivity to warfarin, affecting the required dosage for effective anticoagulation.

CYP2D6 Enzyme and Warfarin

• The CYP2D6 enzyme's variant not associated with warfarin sensitivity requires a lower warfarin dose and represents different metabolic rates.

Gene Mutations VKORC11, VKORC12, and VKORC1*3

• "VKORC1" indicates the specific gene involved in vitamin K metabolism.
• "*1" indicates the wild-type or normal variant of the VKORC1 gene.
• "*2" typically denotes a variant associated with increased sensitivity to warfarin.
• "*3" refers to another variant with a different effect on warfarin metabolism.

Drug Metabolism by CYP2D6

• Approximately 25% to 30% of drugs are at least partially metabolized by the CYP2D6 enzyme.
• Over 100 alleles of the CYP2D6 enzyme have been identified, contributing to diverse drug metabolism profiles.

Drugs Metabolized by CYP2D6

• CYP2D6 metabolizes a variety of drugs, including antidepressants, antipsychotics, and certain opioids.

Haplotype Definition

• Haplotype refers to a group of genes within an organism that are inherited together from a single parent, influencing traits and responses to drugs.

CYP2D6 Haplotype Definition

• CYP2D6 haplotypes are defined by combinations of specific alleles that determine the metabolic capacity of the enzyme.

Metabolizer Types

• Extensive metabolizers have normal metabolic activity, efficiently processing standard drug doses.
• Intermediate metabolizers display reduced metabolic activity, leading to potential drug accumulation and altered response.