What is CYP polymorphism?
Polymorphisms in the CYP family may have had the most impact on the fate of therapeutic drugs. CYP2D6, 2C19, and 2C9 polymorphisms account for the most frequent variations in phase I metabolism of drugs, since almost 80% of drugs in use today are metabolized by these enzymes.
Which is the best definition of the term genetic polymorphism?
Genetic Polymorphism Defined The term relates to the multiple forms of a gene that can exist. Polymorphism promotes diversity and persists over many generations because no single form has an overall advantage or disadvantage over the others in terms of natural selection.
Are CYP genes polymorphic?
CYP 2D6 is a major polymorphic CYP and, as expected, was the greatest contributor of polymorphic alleles in Caucasians. Number of known SNPs per CYP. The pie chart illustrates the number of known SNPs in different CYPs.
What is genetic polymorphism Why is it 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 a polymorphic enzyme?
Enzyme polymorphism may contain two or more variants of an enzyme encoded by a single locus. Although the variant differs slightly in the amino acid sequence, it may affect substrate specificity, enzymatic reaction activity, as well as enzymatic-related transport functions.
How does a polymorphism potentially occur?
DNA polymorphisms are produced by changes in the nucleotide sequence or length. These result from: (i) Variations in the fragment length pattern produced after digesting DNA with restriction enzymes, (ii) Variations in the size of a DNA fragment after PCR amplification, and (iii) Variations in the DNA sequence itself.
What is the importance of genetic polymorphism?
Genetic polymorphisms, through multiple alleles at individual loci, provide a mechanism to tag a gene or a piece of DNA, providing a powerful tool for a variety of investigations.
What does polymorphism mean in pharmacology?
Polymorphism is the ability of solid materials to exist in two or more crystalline forms with different arrangements or conformations of the constituents in the crystal lattice. Hence, polymorphism refers to different structural forms of a chemical substance.
How does genetic polymorphism occur?
Genetic polymorphisms, most commonly occurring as single-nucleotide substitutions in the genomic DNA sequence (also known as SNPs), are heritable genetic differences among individuals; SNPs with frequencies equal to or greater than 5% are regarded as common, whereas those with frequencies lower than 1% are regarded as …
Is cytochrome P450 (CYP) 2D6 activity associated with genetic polymorphism?
DOI: 10.2165/11318030-000000000-00000 Abstract 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.
What does different genetic polymorphism mean?
Genetic Polymorphism—Different Does Not Mean Mutated 1 Genetic Polymorphism Defined. Where monomorphism means having only one form and dimorphism means there are only two forms, the term polymorphism is a very specific term in genetics and biology. 2 Misconceptions. 3 Polymorphism and Mutation. 4 Polymorphism and Enzymes.
What is the clinical significance of CYP2D6*17?
For example, CYP2D6*17 is generally considered as an allele with reduced function, but it displays remarkable variability in its activity towards substrates such as dextromethorphan, risperidone, codeine and haloperidol. The clinical consequence of the CYP2D6 polymorphism can be either occurrence of adverse drug reactions or altered drug response.
What are the variants of CYP2D6?
Among the most important variants are CYP2D6*2, *3, *4, *5, *10, *17 and *41. On the other hand, the CYP2D6 gene is subject to copy number variations that are often associated with the UM phenotype. Marked decreases in drug concentrations have been observed in UMs with tramadol, venlafaxine, morphine, mirtazapine and metoprolol.