GENETIC POLYMORPHISMS OF CYTOCHROME P450 (CYP) 2C9
|
| Allele |
Population
|
Single Nucleotide
Polymorphism
|
Location
|
2C9 Enzyme
Activity
|
Km
|
Vmax
|
| CYP2C9*1 |
General Population
|
Wild-type; 50,720 base pairs |
10q24.1 |
Normal |
28 |
0.22 |
| CYP2C9*2 |
12.8% European Descent
1.3% African Americans |
R144C (3608C→T)
|
Exon 3
|
↓ |
↔ |
↓ |
| CYP2C9*3 |
6.3% European Descent
1.9% African Americans
2-4% Asians
|
I359L (42614A→C)
|
Exon 7
|
↓ |
↓ |
↔ |
| CYP2C9*5 |
0.9-1.8% African
Americans |
D360E (42619C→G)
|
Exon 7
|
↓ |
↑ |
↔ |
| CYP2C9*6 |
0.1-0.75% African
Americans
|
10601delA (818delA)
|
Exon 5
|
Null |
- |
- |
| CYP2C9*11 |
1.5% African American
|
R335W (1003C→T)
|
Exon 7
|
↓ |
↑ |
- |
Note:
C = cystine, D = aspartate, E = glutamate, I = isoleucine, L = leucine,
R = arginine, W = tryptophan; letters in (parenthesis) 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).
Km = the concentration of drug at which half the maximal rate the
reaction occurs; it reflects the binding affinity and rate of the
substrate (medication) to the enzyme. Vmax = the velocity of the reaction at maximal concentrations of the substrate (medication).
References:
- Xie HG, Prasad HC, Kim RB et al. CYP2C9
allelic variants: ethnic distribution and functional significance. Adv
Drug Deliv Rev 2002;54:1257-70. PubMed
- Blaisdell J, Jorge-Nebert LF, Coulter S
et al. Discovery of new potentially defective alleles of human
CYP2C9. Pharmacogenetics 2004;14:527-37. PubMed
- Veenstra DL, You JH, Reider MJ et al.
Association of vitamin K epoxide reductase complex 1 (VKORC1) variants
with warfarin dose in a Hong Kong Chinese patient population.
Pharmacogenet Genomics 2005;15:687-91. PubMed
- Takahashi H, Wilkinson GR, Nutescu EA et
al. Different contributions of polymorphisms in VKORC1 and CYP2C9 to
intra- and inter-populations difference in maintenance dose of warfarin
in Japanese, Caucasians and African-Americans. Pharmacogenet Genomics
2006;16:101-10. PubMed
- Kealey C, Chen Z, Christie J et al.
Warfarin and cytochrome P450 2C9 genotype: possible ethnic variation in
warfarin sensitivity. Pharmacogenomics 2007;8:217-25. PubMed
- Limdi
NA, Arnett DK, Goldstein JA et al. Influence of CYP2C19 and VKORC1 on
warfarin dose, anticoagulation attainment and maintenance among
European-Americans and African-Americans. Pharmacogenomics
2008;9:511-26. PubMed
