What is CYP2D6 polymorphism?

What is CYP2D6 polymorphism?

The polymorphism of the enzyme results in poor, intermediate, efficient or ultrarapid metabolisers (UMs) of CYP2D6 drugs. The polymorphism of CYP2D6 significantly affects the pharmacokinetics of about 50% of the drugs in clinical use, which are CYP2D6 substrates.

What is the function of CYP2D6?

In particular, CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, via the addition or removal of certain functional groups – specifically, hydroxylation, demethylation, and dealkylation. CYP2D6 also activates some prodrugs.

What is the CYP2D6 gene?

CYP2D6 (Cytochrome P450 Family 2 Subfamily D Member 6) is a Protein Coding gene. Diseases associated with CYP2D6 include Drug Metabolism, Poor, Cyp2d6-Related and Neuroleptic Malignant Syndrome. Among its related pathways are Metapathway biotransformation and Propranolol Pathway, Pharmacokinetics.

What are the letters numbers in CYP2D6 represent?

The letters before and after the numbers represent the single nucleotides that make up the DNA sequence and codons to code for an amino acid (A = adenine, C = cytosine, G = guanine, T = thymine).

What are CYP2D6 substrates?

Examples of CYP2D6 substrates can be found in antidepressants (amitriptyline, citalopram, clomipramine, desipramine, doxepin, fluvoxamine, imipramine, maprotiline, mianserin, nortriptyline, fluoxetine, paroxetine), antipsychotics (chlorpromazine, clozapine, haloperidol, perphenazine, risperidone, thioridazine.

What is human Polymorphism?

Polymorphism involves one of two or more variants of a particular DNA sequence. The most common type of polymorphism involves variation at a single base pair. Polymorphisms can also be much larger in size and involve long stretches of DNA.

How common is CYP2D6?

CYP2D6 comprises a relatively small percentage (2% to 6%) of the total cytochrome P-450 in the liver but is involved in the metabolism of many medications (up to 25%). Multiple tricyclic antidepressants, β blockers, haloperidol, sertraline, paroxetine, and thioridazine are among the common drugs metabolized by CYP2D6.

How many drugs are metabolized by CYP2D6?

CYP2D6 metabolizes around 25% of currently prescribed drugs, including various antidepressants, neuroleptics, beta-blockers, opioids, antiemetics, and antiarrhythmics.

Does venlafaxine inhibit CYP2D6?

Conclusions: It is concluded that venlafaxine has a low potential to inhibit the metabolism of substrates for CYP2D6 such as imipramine and desipramine compared with several of the most widely used SSRIs, as well as the metabolism of substrates for several of the other major human hepatic P450s.

What is the clinical significance of cytochrome P450 2D6 polymorphism?

Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I Cytochrome P450 (CYP) 2D6 is one of the most investigated CYPs in relation to genetic polymorphism, but accounts for only a small percentage of all hepatic CYPs (approximately 2-4%). There is a large interindividual variation in the enzyme activity of CYP2D6.

Why is the polymorphism of CYP2D6 important?

The polymorphism of the enzyme results in poor, intermediate, efficient or ultrarapid meta … CYP2D6 is of great importance for the metabolism of clinically used drugs and about 20-25% of those are metabolised by this enzyme. In addition, the enzyme utilises hydroxytryptamines as endogenous substrates.

Does CYP2D6 polymorphism affect EPs in response to risperidone?

The effects of CYP2D6 polymorphism on EPS in response to risperidone are unclear and require further exploration. It is clear that genotypic differences contribute to the discrepancies observed in clinical outcomes.

How many polymorphic CYP2D6 alleles are there?

At present, more than 46 known different major polymorphic CYP2D6 alleles are known. The presence of the highly similar closely located pseudogenes carrying detrimental mutations have through, for example, unequal crossover reactions led to the formation of many of the variant CYP2D6 alleles, which most commonly encode defective gene products.