Pharmacogenomics

34 important questions on Pharmacogenomics

What genetic factors are involved in individual variability in drug response?

Variation in pharmacokinetics, pharmacodynamics and disease etiology.

What environmental factors are involved in individual variability in drug response?

Hormones and lifestyle.

How can genetic variants be caused?

SNPs or CNVs.
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What are Single nucleotide polymorphisms (SNPs)?

A nucelotide change or variation, that can occur within a DNA sequence.

What Are Single Nucleotide Variants (SNVs)?

A single nucleotide substitution, deletion or insertion within a DNA sequence.

What is the difference between a SNP and a SNV?

A SNP is a common single nucleotide variant found in at least 1% of the population, while a SNV refers to any single nucleotide change, regardless of frequency.

What is a Copy Number Variation (CNV)?

When sequences of the genome are repeated, and the number of repeats varies between individuals of the same species.

How does pharmacogenetics look for genes associated with drug response?

By selecting SNPs and CNVs and analyzing metabolizing enzymes, receptors and transporters.

How can we predict the drug response in a individual?

Typing of relevant SNPs in patients before drug administation.

Of which two phases does pharmacokinetics consist?

Functionalization and conjugation reactions.

What does the functionalization phase of pharmacokinetics do?

Oxidation, reduction and hydrolysis of the drug.

What does the conjugation reaction phase of pharmacokinetics do?

Adding a highly polar conjugation functional group to the polar functional group produced by phase I enzymes.

Why are medicines hydrophilic?

So they can be excreted in the urine.

What is cytochrome P450 2D6?

An enzyme that metabolizes many drugs and endogenous substances.

Where is CYP2D6 primarily expressed?

The liver.

How does CYP2D6 hydroxylate drugs?

By adding a OH group.

By what gene is Cytochrome P450 2D6 encoded?

CYP2D6

How can metabolizer phenotypes be predicted?

By the combination of alleles present in an individual.

What is increased enzyme activity most often due to?

Gene copy number variations, namely the presence of one or more functional gene copies.

What can SNPs in CYP2D6 cause?

Poor metabolism, higher plasma concentration and a lower urinary concentration.

How do thiopurines work?

They stop cell division.

What kind of adverse events can be caused by thiopurines?

Bone marrow suppression and damage to the liver (hepatotoxicity).

For which diseases can thiopurines be used?

Crohns disease and ulcerative colitis

How can a thiopurine treatment be done?

With Azacitidine.

How can a thiopurine treatment be monitored?

Bloodcell count and liver function.

How can optimization of the thiopurine treatment be done?

Thiopurine methyltransferase genotyping, enzyme activity and thiopurine metabolite monitoring.

What is Thiopurine methyltransferase (TPMT)?

The enzyme that metabolizes thiopurine drugs.

What is Inflammatory bowel disease (IBD)?

A group of inflammatory conditions of the colon and small intestine.

What are examples of inflammatory bowel diseases?

Crohn's diease and ulcerative colitis.

What is a side effect of Ribavirin?

Anemia.

How is the anemia with Ribavirin caused?

To extensive RBV accumulation in erythrocytes.

What is Dihydropyrimidine dehydrogenase deficiency (DPYD)?

A disease in which there is absent or significantly decreased activity of dihydropyrimidine dehydrogenase.

What is the function of dihydropyrimidine dehydrogenase?

An enzyme involved in the metabolism of uracil and thymine (pyrimidines).

How can pharmacogenetics be used in the daily practice?

Choice of medication, dosage of medication or additional medication to counteract adverse reactions.

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