GENETIC POLYMORPHISMS OF CYTOCHROME P450 (CYP) 1A2 ©2011 Pharmacology Weekly, Inc.
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 codons 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

Chida M, Yokoi T, Fukui T et al.  Detection of three genetic polymorphisms in the 5'-flanking region and intron 1 of human CYP1A2 in the Japanese population.  Jpn J Cancer Res 1999;90:899-902.  PubMed

Chen X, Wang L, Zhi L et al.  The G-3113A polymorphism in CYP1A2 affects the caffeine metabolic ratio in Chinese population.  Clin Pharmacol Ther  2005;78:249-59.  PubMed

Pavanello S, Pulliero A, Lupi S et al.  Influence of the genetic polymorphism in the 5'-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers.  Mutat Res 2005;587:59-66.  PubMed

Akillu E, Carrillo JA, Makonnen E et al. Genetic polymorphism of CYP1A2 in Ethiopians affecting induction and expression: characterization of novel haplotypes with single-nucleotide polymorphisms in intron 1.  Mol Pharmacol 2003;64:659-69.  PubMed 

Zhou SF, Yang LP, Zhou ZW et al.  Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2.  AAPS J  2009;11:481-94.  PubMed

Huang JD, Guo WC, Lai MD et al.  Detection of a novel cytochrome P-450 1A2 polymorphism (F21L) in Chinese.  Drug Metab Dispos 1999;27:98-101. PubMed

Pucci L, Geppetti A, Maggini V et al.  CYP1A2 F21L and F186L polymorphism in an Italian population sample.  Drug Metab Pharmacokinet  2007;22:220-2.  PubMed

Chevalier D, Cauffiez C, Allorge D, et al. Five novel natural allelic variants—951A>C, 1042G>A (D348N), 1156A>T (I386F), 1217G>A (C406Y) and 1291C>T (C431Y)—of the human CYP1A2 gene in a French Caucasian population. Hum Mutat  2001;17:355-356.  PubMed

Zhou H, Josephy PD, Kim D et al.  Functional characterization of four allelic variants of human cytochrome P450 1A2.  Arch Biochem Biophys 2004;422:23-30.  PubMed

Allorge D, Chevalier D, Lo-Guidice JM et al.  Identification of a novel splice-site mutation in the CYP1A2 gene.  Br J Clin Pharmacol  2003;56:341-4.  PubMed

Soyama A, Saito Y, Hanioka N et al.  Single nucleotide polymorphisms and haplotypes of CYP1A2 in a Japanese population.  Drug Metab Pharmacokinet  2005 20:24-33.  PubMed

Uslu A, Ogus C, Ozdemir T et al.  The effect of CYP1A2 gene polymorphisms on Theophylline metabolism and chronic obstructive pulmonary disease in Turkish patients.  BMB Rep 2010;43:530-4.  PubMed

Shimada 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 Japanese and 30 Caucasians. J Pharmacol Exp Ther  1994;270:414-423.  PubMed

Disclaimer:  For more information click here

©2011 Pharmacology Weekly Inc.  All Rights Reserved.