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GENETIC POLYMORPHISMS OF CYTOCHROME P450 (CYP) 1A2
|
|
| Allele |
Population
|
Single Nucleotide
Polymorphism
|
Location
|
CYP1A2
Activity
|
Notes
|
CYP1A2*1
|
General Population |
Wild-type; 7.8kb
|
15q24.1
|
normal
|
Contains 7 exons & 6
introns that code for a
515-residue protein with
a MW of 58,294 Da |
|
CYP1A1*1B
|
Chinese
French caucasians 35%
|
C5347T (N516N)
|
Exon 7 |
unknown
|
Impact not known
|
CYP1A2*1C
|
Japanese |
G-3860A
|
Enchancer
|
↓
|
Associated with ↓
inducibility of 1A2
|
CYP1A2*1D
|
Turkish 92%
Japanese 42-44%
Egyptians 40%
|
T-2467delT |
Enhancer
|
unknown
|
Impact not known
|
CYP1A2*1E
|
Japanese 42%
Caucasians 4.8%
|
T-739G
|
Intron 1
|
unknown
|
Impact not known
|
CYP1A2*1F
|
British whites 33%
German whites 32%
|
C-163A
|
Intron 1
|
↑
|
Associated with ↑1A2
production/activity
|
CYP1A2*1J
|
Saudi Arabains 5.9%
Spaniards 1.3%
|
-740G; -164A
|
Intron 1
|
unknown |
Impact currently
unknown
|
CYP1A2*1K
|
Saudi Arabians 3.6%
Spaniards 0.5%
|
-730T; -740G;
-164A
|
Intron 1 |
↓
|
May disrupt transcription
factor binding that leads
to ↓transcription |
CYP1A2*2
|
Chinese 0.32%
|
C2866G (F21L)
|
Exon 2
|
unknown
|
Impact not known |
CYP1A2*3
|
French ≤ 0.5-1% |
T5347T (D348N)
|
Exon 4
|
↓
|
↓gene expression |
CYP1A2*4
|
French ≤ 0.5-1%
|
A2499T (I383F) |
Exon5 |
↓
|
↓gene expression
|
CYP1A2*5
|
French ≤ 0.5-1%
|
G3497A (C406Y) |
Exon 6
|
unknown
|
Impact not known
|
CYP1A2*6
|
French ≤ 0.5-1%
|
G5090T (R431W)
|
Exon 7
|
↓
|
↓gene expression
|
CYP1A2*7
|
NR
|
G3533A
|
Intron 6
|
↓
|
Splicing defect in gene
|
CYP1A2*8
|
Japanese < 1%
|
G5166A (R456H)
|
Exon 7
|
↓
|
Impact in-vivo not known |
CYP1A2*9
|
Japanese < 1%
|
C248T (T38M)
|
Exon 2
|
unknown |
Impact not known
|
CYP1A2*10
|
Japanese < 1%
|
G502C (E168Q)
|
Exon 2
|
unknown
|
Impact not known |
CYP1A2*11
|
Japanese < 1%
|
C558A (F186L)
|
Exon 2
|
↓
|
Impact in-vivo not known
|
CYP1A2*12
|
Japanese < 1%
|
A634T (S212C)
|
Exon 2
|
unknown
|
Impact in-vivo not known
|
CYP1A2*13
|
Japanese < 1%
|
G1514A (G299S)
|
Exon 3
|
unknown
|
Impact in-vivo not known
|
CYP1A2*14
|
Japanese < 1%
|
C5112T (T438I)
|
Exon 7
|
normal
|
Impact in-vivo not known |
CYP1A2*15
|
Japanese < 1%
|
C125G (P42R)
|
Exon 2
|
↓
|
Impact in-vivo not known
|
CYP1A2*16
|
Japanese < 1%
|
G2473A (R377Q)
|
Exon 5
|
↓
|
Impact in-vivo not known
|
|
The letters before and after the numbers represent the single nucleotides that make up the DNA sequence and to code for an
amino acid (A = adenine, C = cytosine, G = guanine, T = thymine).
Amino acids represented: (C = cysteine, D = aspartate, F =
phenyalanine, G = glycine, H = histidine, K = lysine, L = leucine, M =
methionine, N = asparagine, P =
proline, Q = glutamine, R = arginine, S = serine, T = threonine, V = valine, W = tryptophan, Y = tyrosine). NR = not reported.
REFERENCES:
-
Zhou SF, Wang B, Yang LP et al. Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. Drug Metab Rev 2010;42:268-354. PubMed
- Sachse C, Bhambra U, Smith G et al.
Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal
cancer patients and controls: allele frequencies, linkage
disequilibrium and influence on caffeine metabolism. Br J Clin Pharmacol 2003;55:68-76. PubMed
- Sachse C, Brockmoller J, Bauer S et al. Functional significant of a C->A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 1999;47:445-9. Pubmed
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Influence of the genetic polymorphism in the 5'-noncoding region of the
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The effect of CYP1A2 gene polymorphisms on Theophylline metabolism and
chronic obstructive pulmonary disease in Turkish patients. BMB Rep 2010;43:530-4. PubMed
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T, Yamazaki H, Mimura M et al.Interindividual variations in human liver
cytochrome P-450 enzymes involved in the oxidation of drugs,
carcinogens and toxic chemicals: studies with liver microsomes of 30
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