How does genetic polymorphism affects drug metabolism?

How does genetic polymorphism affects drug metabolism?

Genetic polymorphisms have been identified for many drug-metabolizing enzymes, including the cytochrome P450 (CYP450) enzymes. This gives rise to distinct population phenotypes of persons who have metabolism capabilities ranging from extremely poor to extremely fast.

How is SNP related to individual drug response?

Single Nucleotide Polymorphisms (SNPs) holds the key in defining the risk of an individual’s susceptibility to various illnesses and response to drugs. There is an ongoing process of identifying the common, biologically relevant SNPs, in particular those that are associated with the risk of disease.

Why is genetic polymorphism important in drug dosing?

Genetic polymorphisms in drug transporters such as P-gp may predict the partitioning characteristics of a drug between cells and plasma. This may aid either in determining the therapeutic range or avoiding specific drugs with a particularly high risk of efficacy failure or toxicity.

What is the role of SNPs?

Most commonly, SNPs are found in the DNA between genes. They can act as biological markers, helping scientists locate genes that are associated with disease. When SNPs occur within a gene or in a regulatory region near a gene, they may play a more direct role in disease by affecting the gene’s function.

How does genetics affect drug metabolism?

Genetic variability of drug metabolizing enzymes and drug transporters has been associated with interindividual differences in pharmacokinetics and pharmacodynamics. Such differences may result in variation in drug efficacy, safety and treatment outcomes in a number of frequently prescribed drugs3.

What factors can affect metabolism of drugs?

Physiological factors that can influence drug metabolism include age, individual variation (e.g., pharmacogenetics), enterohepatic circulation, nutrition, intestinal flora, or sex differences. In general, drugs are metabolized more slowly in fetal, neonatal and elderly humans and animals than in adults.

How genetic variations can affect the metabolism of a drug?

Genetic polymorphisms in drug transporters and phase-1 drug-metabolizing enzymes can alter the pharmacokinetic and pharmacokinetic properties of the administered drugs, their metabolites or both at the target site, resulting in variability in drug responses.

How a genetic variation will affect drug response?

Single variants in genes not involved in drug metabolism can also confer high risk for variable drug responses. These may involve variants in genes encoding the target molecules or pathways with which drugs interact, or those encoding genes unrelated to the therapeutic effect.

Why do we have genes for drug metabolism?

Drug transporters primarily control the movement of all drugs and their active or inactive metabolites into or out of cells. Therefore, polymorphisms of drug transporter genes can modify the absorption, distribution, and excretion rates, and ultimately safety and efficacy of the administered drugs.

What factors affect metabolism of a drug?

Dose, frequency, route of administration, tissue distribution and protein binding of the drug affect its metabolism. Pathological factors can also influence drug metabolism, including liver, kidney, or heart diseases.

How do SNPs alter function?

SNPs may change the encoded amino acids (nonsynonymous) or can be silent (synonymous) or simply occur in the noncoding regions. They may influence promoter activity (gene expression), messenger RNA (mRNA) conformation (stability), and subcellular localization of mRNAs and/or proteins and hence may produce disease.

What factors can affect drug metabolism?

How does polymorphism affect drug absorption?

One of the major causes of interindividual variation of drug effects is genetic variation of drug metabolism. Genetic polymorphisms of drug-metabolizing enzymes give rise to distinct subgroups in the population that differ in their ability to perform certain drug biotransformation reactions.

What are two internal factors that affect metabolism of a drug?

Internal: species, genetic (strain), sex, age, hormones, pregnancy, disease. External: diet, environment.

What influences drug metabolism?

Individual drug metabolism rates are influenced by genetic factors, coexisting disorders (particularly chronic liver disorders and advanced heart failure), and drug interactions (especially those involving induction or inhibition of metabolism). For many drugs, metabolism occurs in 2 phases.

What are 2 internal factors that affect metabolism of a drug?

Which factor is most important for drug metabolism?

The most important enzyme system of phase I metabolism is cytochrome P-450 (CYP450), a microsomal superfamily of isoenzymes that catalyzes the oxidation of many drugs.

How do SNPs affect gene regulation?

How do SNPs affect proteins?

When arising in genes, SNPs can impact on mRNA splicing, nucleo-cytoplasmic export, stability, and translation. When present within a coding sequence and leading to an amino acid change (referred to as a non-synonymous SNP or mutation), they can modify the protein’s activity.