GENETIC POLYMORPHISMS OF CYTOCHROME P450 (CYP) 2C19
|
Allele
|
Population
|
Single Nucleotide
Polymorphism
|
Location
|
Activity
|
Notes
|
| CYP2C19*1 |
General Population
|
Wild-type; 50,720bp |
10q24.1-3 |
Normal |
Extensive metabolizer
|
| CYP2C19*2 |
2-5% Caucasians
18-23% Japanese
|
40bp deletion
(681G→A)
|
Exon 5
|
↓ |
Poor metabolizer
|
| CYP2C19*3 |
13% Islands of
Vanuatu
|
W212X(636G→A) |
Exon 4
|
↓ |
Poor metabolizer;
premature stop codon
|
| CYP2C19*4 |
0.6-3% Caucasians
|
M1V (Mutation in
initiation codon
A→G
|
Initiation
codon
|
↓ |
Poor metabolizer,
Defect in initiation
codon |
| CYP2C19*5 |
Low in both Chinese
& Japanese
|
R433W (1297C→T) |
Exon 9 |
↓ |
Poor metabolizer
|
| CYP2C19*17 |
18% Ethiopians
& Swedes,
1.3% Japanese,
0.64% Chinese
|
C806T (3402C→T)
|
5'-flanking
region
|
↑ |
Ultra-rapid metabolizer
Increased 2C19 gene
transcription |
Note: A = adenine (nucleotide), C = cystine (nucleotide), G = guanine (nucleotide), M = methionine (amino acid), R = arginine (amino acid), T = thymine (nucleotide); V = valine (amino acid); W = tryptophan (amino acid); X = termination codon.
References:
- Meier UT, Meyer UA. Genetic
polymorophism of human cytochrome P-450 (S)-mephenytoin 4-hydroxylase:
studies with human autoantibodies suggest a functionally altered
cytochrome P-450 isoenzyme as cause of the genetic deficiency.
Biochemistry 1987;26:8466-8474. PubMed
- De Morais SMF, Wilkinson GR, Blaisdell J
et al. Identification of a new genetic defect responsible for the
polymorphism of (S)-mephenytoin metabolism in Japanses. Molec
Pharmacol 1994;46:594-8. PubMed
- De Morais SMF, Wilkinson GR, Blaisdell J
et al. The major genetic defect responsible for the polymoprhism of
S-mephenytoin metabolism in humans. J Biol Chem 1994;269:15419-15422. PubMed
- Kaneko A, Kaneko O, Taleo G et al. High
frequencies of CYP2C19 mutations and poor metabolism of proguanil in
Vanuatu. Lancet 1997;349:921-2. PubMed
- Ferguson RJ, DeMorais SMF, Benhamou S et
al. A new genetic defect in human CYP2C19: mutation of the initiation
codon is responsible for poor metabolism of S-mephenytoin. J Pharmacol
Exp Ther 1998;284:356-361. PubMed
- Sim SC, Risinger C, Dahl ML et al. A
common novel CYP2C19 gene variant causes ultra-rapid drug metabolism
relevant for the drug response to proton pump inhibitors and
antidepressants. Clin Pharmacol Ther 2006;79:103-113. PubMed
- Sugimoto K, Uno T, Yamazaki H et al.
Limited frequency of the CYP2C19*17 allele and its major role n a
Japanese population. Br J Clin Pharmacol 2008;65:437-39. PubMed
