Search tips
Search criteria 


Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Pharmacogenet Genomics. Author manuscript; available in PMC 2013 January 1.
Published in final edited form as:
PMCID: PMC3346273

PharmGKB summary: very important pharmacogene information for CYP1A2


CYP1A2 is part of the cytochrome P450 (CYP) family of drug-metabolizing enzymes. The CYP1A2 gene is found in a cluster with CYP1A1 and CYP1B1 on chromosome 15 [1]. CYP1A2 and CYP1A1 share a 5′-flanking region of approximately 23 kb, which contains shared regulatory elements, although the genes are positioned back to back and transcription occurs in opposite directions [2]. The CYP1A2 gene spans around 7.8 kb and features seven exons and six introns, the first being a 55-bp-long noncoding exon. CYP1A2 is a 515-residue protein with a molecular mass of 58 294 Da [1].

CYP1A2 is an important metabolizing enzyme in the liver, comprising approximately 13% of all CYP protein (compared with CYP2D6 at 2%) [3]. There are over 100 substrates reported for CYP1A2, including many clinically important drugs (e.g. clozapine, tacrine), procarcinogens (e.g. benzopyrene and aflatoxin b1), and endogenous substrates (e.g. steroids and arachidonic acid) [1]. However, compared with other CYPs, there have been relatively few reports of PGx relationships. This may be explained by the smaller number of prescription drugs for which CYP1A2 is a metabolizing enzyme (9% compared with 37% for CYP3A4/5, 17% for CYP2C9, and 15% for CYP2D6) and by the fact that for many drugs CYP1A2 is not the sole metabolizing enzyme, nor is it active at the rate-limiting step [4]. This may also be because of fewer reported variants that impact CYP1A2 activity. The genetic component of variation in CYP1A2 activity is estimated at up to 75%, with environmental factors making up the remaining difference, such as smoking (induction) and oral contraceptive use in women (inhibition) [5]. However, a recent pathway-based analysis in human liver samples estimated that the genetic variation of CYP1A2 activity may only account for 42, 38, and 33% of the catalytic activity, protein expression, and mRNA levels, respectively [6]. Given the predominant role of CYP1A2 in activation of toxic xenobiotics compared with its metabolism of prescription drugs, there are many epidemiological reports examining the role of variant CYP1A2, metabolism of procarcinogens, and cancer risk.

CYP1A2 regulation

CYP1A2 is constitutively highly expressed in liver and is inducible in the liver, lung, pancreas, gastrointestinal tract, and brain [7]. Drug–drug interactions and interactions with smoking have been reported to alter drug response [1]. Smoking, dietary cruciferous vegetables, polyamine hydrocarbons from grilled meat, and omeprazole and other proton pump inhibitors have been [3] shown to induce CYP1A2 [8]. Oral contraceptives, fluvoxamine, and fluoroquinolone antibiotics reduce expression [8].

The shared promoter of CYP1A2 and CYP1A1 has at least 13 response elements for the aryl hydrocarbon receptor (AHR) [7] (see the very important pharmacogene information for AHR at The transcription factor binding sites are palindromic and may therefore influence transcription in both directions, that is, either the CYP1A2 or the CYP1A1 promoter. These elements are involved in the activation response to xenobiotics, cruciferous vegetables, and polyamine hydrocarbons. Studies examining variants in the promoter have tended to look at their effects on the gene they are closest to.

Omeprazole and primaquine activate both human CYP1A1 and CYP1A2 expression through the common regulatory region in a mechanism that may be independent of AHR [9]. Lansoprazole and albendazole also activate CYP1A1 and CYP1A2, although they preferentially induce CYP1A1 [9]. The nuclear receptor CAR (coded for by NR1I3) transactivates human CYP1A1 and CYP1A2 in human hepatocytes through the common cis-element ER8 [10].

CYP1A2 variation

Many variants have been reported for CYP1A2, with some having an impact on drug metabolism. For a full list of variants, see the CYP allele nomenclature. No copy number polymorphisms for CYP1A2 have been reported to date [11]. There is approximately 40% variability in liver expression of the CYP1A2 gene and 60% variability in caffeine metabolism, the probe drug used most often for CYP1A2 [8]. Unlike other drug-metabolizing CYPs, few variants that could clearly explain the phenotypic variability in CYP1A2 gene expression or inducibility have been identified [12]. The coding sequence variants reported have been seen at very low frequency in White and Asian populations [12]. A recent paper examining CYP1A2 variation in Ethiopians suggested that because of the overall greater incidence of variation, including some novel presumable deleterious variants, there could be some individuals devoid of any CYP1A2 activity in this population [11].

There is some variability of numbering of variants in the literature. PharmGKB uses the numbering from the CYP allele nomenclature. For details on selected haplotypes and variants of pharmacogenomic interest, see below.

CYP1A2 drug metabolism

Caffeine is the main probe drug used to assess CYP1A2 activity in vivo. Theophylline and melatonin are also sometimes used as probe drugs, whereas in-vitro studies often use phenacetin [8]. CYP1A2 is responsible for more than 95% of the primary metabolism of caffeine [13]. For details of the metabolism of caffeine and the genes involved see Some studies have also examined caffeine as a modulator of disease etiology, looking at intake of caffeine containing foods and beverages with respect to disease risk (see individual variant descriptions for more details). Two recent independent genome-wide association studies have looked at the influence of variants on caffeine intake. Interestingly, both found associated variants in the regulatory region of CYP1A2 (rs2472304 and rs2472297) and in its regulator AHR (rs4410790 and rs6968865) [14,15].

CYP1A2 has been shown to be important for dosing of several antipsychotics and for assessing both drug efficacy and adverse drug reactions. CYP1A2 is the main CYP isoform involved in clozapine metabolism [16]. Case studies have shown ultrarapid metabolizers of clozapine that presented as resistant to treatment. Improved patient outcomes were obtained by increased clozapine doses and coadministration with the CYP1A2 inhibitor fluvoxamine [17,18]. There have also been discussions on the interaction of smoking and drug response and the potential dangers of smoking cessation in patients with schizophrenia [19].

CYP1A2 also influences the antithrombotic drug clopidogrel. Smoking increases clopidogrel-mediated platelet inhibition [20,21]. This is likely by induction of CYP1A2, causing it to play a larger role in the generation of active drugs.

Important haplotypes


This is considered the reference or ‘wild-type’ allele to which all variants are compared.


The CYP1A2*1F haplotype has been associated in many studies with an altered phenotype [12]. Generally, it is considered to have increased activity (ultrarapid metabolizer) because of increased induction of expression. The phenotype effect is observed only in the presence of an inducer, such as smoking or heavy coffee consumption [22,23].

There is some confusion in the literature regarding the designation of this haplotype [24]. The variant that defines this haplotype, CYP1A2: −163C> A (rs762551), has different frequencies in different populations and the assignment of major and minor alleles therefore varies. Most publications have listed *1Fas C > A [24], but others have A > C [25]. Most studies that reported results for CYP1A2*1F actually only measured rs762551; as rs762551:C > A is part of other haplotypes (CYP1A2*1J, *1K, *17, *21 and several other predicted haplotypes), we have included those results in the discussion of rs762551.

A study of CYP1A2*1F in which they excluded other haplotypes containing rs762551A showed that rs762551AA was associated with increased metabolism of caffeine in Swedish smokers [12] as well as in Swedish and Serbian heavy coffee consumers [22]. Other haplotypes that included rs762551:C > A did not have a significantly altered metabolism of caffeine [12].

A study of nonsmoking healthy individuals taking omeprazole showed increased induction of caffeine metabolism in CYP1A2*1F/*1F homozygotes compared with CYP1A2*1C/*1F heterozygotes [26].


The defining and only single-nucleotide polymorphism (SNP) for this haplotype is −3860G > A (rs2069514), also seen in the literature as −2964G > A [27]. This haplotype has been reported to have decreased activity. See important variant rs2069514:G > A for more details.


There are three variants that define this haplotype: −739T > G (rs2069526), −729C > T (rs12720461), and −163C > A (rs762551). This allele was reported originally in Ethiopians at a frequency of 3% (n = 173), in Spaniards at a frequency of 0.5% (n = 117), and in Saudi Arabians at 3.6% (n = 136) [28]. CYP1A2*1K allele had significantly reduced CYP1A2 activity in nonsmokers compared with *1A or *1F, using caffeine as a probe substrate [28]. This haplotype has not been observed in Japanese (n = 350) [29] and Koreans (n = 50) and occurs at a very low frequency in Swedes (n = 193, 0.3%) [12]. Therefore, follow-up functional studies have been unable to confirm effects on drug metabolism.

Important variants

rs762551, CYP1A2: - 163C > A, NM_000761.3:c.-9-154C > A

This SNP is the most well-studied genetic variant in CYP1A2. It is the sole variant of the CYP1A2*1F haplotype and found with other variants in several haplotypes (*1J, *1K, *21, and others that have not been confirmed). It is located in the intron between the noncoding exon 1 and exon 2, where the coding sequence begins [8]. The frequency of rs762551:C > A varies widely with populations: the C allele frequencies range from 0.3 to 0.39 in Asians, from 0.4 to 0.51 in Blacks or African Americans, and from 0.29 to 0.33 in Whites [8].

This variant was reported as showing increased caffeine metabolism in Caucasian smokers with the AA genotype compared with the CA and CC genotypes, but the effect was not seen in nonsmokers [30]. This effect was also not seen in pregnant Swedish smokers [31]. In a study on Ethiopian smokers, the CYP1A2*1F haplotype (i.e. solely rs762551) was not associated with increased caffeine metabolism compared with CYP1A1*1A; however, CY-P1A2*1K, rs762551:C > A plus rs2069526:T > G, and rs12720461:C > T showed decreased metabolism [28]. A study on Japanese patients and healthy volunteers found no association of this variant when challenged with both theophyline and caffeine [29]. In a study of CYP1A2*1F, in which other haplotypes containing rs762551:C > A were excluded, rs762551AA was associated with increased metabolism of caffeine in Swedish smokers [12]. This suggests that rs762551:C > A may not be the causative variant and its effects may differ in different populations because of differences in linkage, diet, drug, or environmental exposures.

A few studies have examined dietary caffeine effects on disease risk. In a study on South Americans, the authors stated that ‘slow’ caffeine metabolizers genotyped for the rs762551:C > A variant had increased risk of myocardial infarction [25]. There was some confusion because of incorrect use of nomenclature in this paper, which was later clarified in a letter stating that the AA genotype was considered ‘fast’ caffeine metabolizer and the C allele ‘slow’ [24,32]; however, this is still an oversimplification because, as mentioned above, the fast metabolizer phenotype for rs762551AA is only observed under induction by smoking or high habitual coffee intake. Some studies have examined the role of caffeinated coffee intake and protection against Parkinson’s disease in conjunction with variant CYP1A2. One study showed that individuals with the CC genotype had decreased risk [33], but other studies have not observed this [34,35].

Several papers have reported the influence of rs762551:C > A on response or adverse effects with antipsychotic drugs; with the A allele leading to lower serum drug concentrations and higher risk for nonresponse and the C allele leading to higher plasma drug levels and greater risk for side effects. Various case studies have shown that individuals with the AA genotype are at risk for nonresponse to clozapine (see overview section) [17,18]. Individuals with the AA genotype receiving olanzepine also have lower serum drug concentrations and decreased treatment efficacy [36]. Some studies have associated the CC genotype with increased incidence or severity of tardive dyskinesia in people with schizophrenia treated with antipsychotics. However, other studies did not see this effect and a meta-analysis also failed to see any association even when accounting for smoking behavior and ethnicity [37-42]. The C allele is associated with increased QT interval in patients with schizophrenia treated with antipsychotics, in which CYP1A2 contributes to their metabolism, namely chlorpromazine, fluphenazine, trifluoperazine, and thioridazine [43].

The A allele was associated with an increased dose of paroxetine and also with increased likelihood of experiencing drug-related fatigue in Han Chinese patients with Major Depressive Disorder [44].

rs2069514, CYP1A2: - 3860G > A

Originally called −2964G > A [27], the CYP nomenclature site now calls it −3860G > A; this SNP is also known as CYP1A2*1C. It is found at frequencies of 7% in Blacks or African Americans, at 6–25% in Asians, and at 0.4–1% in Whites [23,29,41,4547]. This variant was associated with decreased rate of caffeine demethylation in Japanese smokers but not in nonsmokers. The variant alters a transcription factor binding site in the gene promoter, although the factor was not defined [27].

The A allele was associated with increased severity of tardive dyskinesia in Indian smokers with schizophrenia taking typical antipsychotics [41]. However, after restricting the analysis by smoking and drug type, the sample size was very small. This association was not seen in a Japanese population [48].

The A allele is associated with lower clearance of theophylline in a study on Japanese nonsmoking asthmatics [27]. However, a later study found no association of this variant when challenged with both theophyline and caffeine [29].

rs12720461, CYP1A2: - 729C > T

Also called CYP1A2: −730C > T, this variant was shown in vitro to affect binding of an E-twenty six transcription factor [28]. Reporter constructs with this variant had lower inducibility with 2,3,7,8-tetrachlorodibenzo-p-dioxin in human hepatoma cells and may affect bioactivation and sensitivity to carcinogens [28]. This may also explain the lower caffeine metabolism seen for the CYP1A2*1K haplotype, which is the only haplotype that contains this variant.


Understanding the pharmacogenomic effects of CYP1A2 variation is still at an early stage compared with that of other CYP enzymes. There is a need for well-defined phenotype groups so that studies have adequate power to discern effects of genomic variants against the background of potential inducers (caffeine, smoking, diet, etc.). For example, the studies on associations of CYP1A2 with antipsychotics have had conflicting results; however, larger studies in which the drugs are specified, or limited to those primarily metabolized by CYP1A2, and that provides details of all inducers and CYP2D6 status may provide a clearer picture. There is also the need to fully assess all other variants before assigning a haplotype. Early studies may have mistakenly categorized individuals as CYP1A1*1A or *1F. Recent studies have identified several new predicted haplotypes that include rs762551, including variants such as rs2472304 (2159G > A) and rs2470890 (5347C > T) that were found at high frequencies in an Ethiopian population (43 and 33%, respectively) and at moderate frequencies in a Japanese population (17.4 and 23%, respectively) [11,49]. There is a great need for functional studies to determine the impact of these variants and define whether measurement of rs762551 alone in PGx studies misses the full picture. Caution should be used when inferring activity with probe substrates to other drugs as there may be different autoinductions of CYP1A2.

The presence of allelic imbalance in CYP1A2 expression and the importance of epigenetic genetic variation in influencing CYP1A2 mRNA expression and enzyme activity in vitro using human liver were reported recently [50]. Apart from genetic variation, epigenetic and environmental factors play a role in determining interindividual and interethnic variability in CYP1A2 expression and enzyme activity.

This PharmGKB summary briefly discusses the very important pharmacogene CYP1A2 and its haplotypes and variants that can influence drug responses. A fully interactive version of this short review, with links to individual paper annotations and population descriptions, can be found at


This work is supported by the NIH/NIGMS (R24 GM61374).


Conflicts of interest

There are no conflicts of interest.


1. Zhou SF, Yang LP, Zhou ZW, Liu YH, Chan E. Insights into the substrate specificity, inhibitors, regulation, and polymorphisms and the clinical impact of human cytochrome P450 1A2. AAPS J. 2009;11:481–494. [PMC free article] [PubMed]
2. Ueda R, Iketaki H, Nagata K, Kimura S, Gonzalez FJ, Kusano K, et al. A common regulatory region functions bidirectionally in transcriptional activation of the human CYP1A1 and CYP1A2 genes. Mol Pharmacol. 2006;69:1924–1930. [PubMed]
3. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. 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]
4. Zanger UM, Turpeinen M, Klein K, Schwab M. Functional pharmacogenetics/ genomics of human cytochromes P450 involved in drug biotransformation. Anal Bioanal Chem. 2008;392:1093–1108. [PubMed]
5. Rasmussen BB, Brix TH, Kyvik KO, Brosen K. The interindividual differences in the 3-demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors. Pharmacogenetics. 2002;12:473–478. [PubMed]
6. Klein K, Winter S, Turpeinen M, Schwab M, Zanger UM. Pathway-targeted pharmacogenomics of CYP1A2 in human liver. Front Pharmacol. 2010;1:129. [PMC free article] [PubMed]
7. Jorge-Nebert LF, Jiang Z, Chakraborty R, Watson J, Jin L, McGarvey ST, et al. Analysis of human CYP1A1 and CYP1A2 genes and their shared bidirectional promoter in eight world populations. Hum Mutat. 2010;31:27–40. [PMC free article] [PubMed]
8. Gunes A, Dahl ML. Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms. Pharmacogenomics. 2008;9:625–637. [PubMed]
9. Yoshinari K, Ueda R, Kusano K, Yoshimura T, Nagata K, Yamazoe Y. Omeprazole transactivates human CYP1A1 and CYP1A2 expression through the common regulatory region containing multiple xenobiotic-responsive elements. Biochem Pharmacol. 2008;76:139–145. [PubMed]
10. Yoshinari K, Yoda N, Toriyabe T, Yamazoe Y. Constitutive androstane receptor transcriptionally activates human CYP1A1 and CYP1A2 genes through a common regulatory element in the 5′-flanking region. Biochem Pharmacol. 2010;79:261–269. [PubMed]
11. Browning SL, Tarekegn A, Bekele E, Bradman N, Thomas MG. CYP1A2 is more variable than previously thought: a genomic biography of the gene behind the human drug-metabolizing enzyme. Pharmacogenet Genomics. 2010;20:647–664. [PubMed]
12. Ghotbi R, Christensen M, Roh HK, Ingelman-Sundberg M, Aklillu E, Bertilsson L. Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and Koreans. Eur J Clin Pharmacol. 2007;63:537–546. [PubMed]
13. Kalow W, Tang BK. The use of caffeine for enzyme assays: a critical appraisal. Clin Pharmacol Ther. 1993;53:503–514. [PubMed]
14. Cornelis MC, Monda KL, Yu K, Paynter N, Azzato EM, Bennett SN, et al. Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption. PLoS Genet. 2011;7:e1002033. [PMC free article] [PubMed]
15. Sulem P, Gudbjartsson DF, Geller F, Prokopenko I, Feenstra B, Aben KK, et al. Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption. Hum Mol Genet. 2011;20:2071–2077. [PMC free article] [PubMed]
16. Jaquenoud Sirot E, Knezevic B, Morena GP, Harenberg S, Oneda B, Crettol S, et al. ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine. J Clin Psychopharmacol. 2009;29:319–326. [PubMed]
17. Ozdemir V, Kalow W, Okey AB, Lam MS, Albers LJ, Reist C, et al. Treatment-resistance to clozapine in association with ultrarapid CYP1A2 activity and the C– >A polymorphism in intron 1 of the CYP1A2 gene: effect of grapefruit juice and low-dose fluvoxamine. J Clin Psychopharmacol. 2001;21:603–607. [PubMed]
18. Eap CB, Bender S, Jaquenoud Sirot E, Cucchia G, Jonzier-Perey M, Baumann P, et al. Nonresponse to clozapine and ultrarapid CYP1A2 activity: clinical data and analysis of CYP1A2 gene. J Clin Psychopharmacol. 2004;24:214–219. [PubMed]
19. Skogh E, Bengtsson F, Nordin C. Could discontinuing smoking be hazardous for patients administered clozapine medication? A case report. Ther Drug Monit. 1999;21:580–582. [PubMed]
20. Bliden KP, Dichiara J, Lawal L, Singla A, Antonino MJ, Baker BA, et al. The association of cigarette smoking with enhanced platelet inhibition by clopidogrel. J Am Coll Cardiol. 2008;52:531–533. [PubMed]
21. Gremmel T, Steiner S, Seidinger D, Koppensteiner R, Panzer S, Kopp CW. Smoking promotes clopidogrel-mediated platelet inhibition in patients receiving dual antiplatelet therapy. Thromb Res. 2009;124:588–591. [PubMed]
22. Djordjevic N, Ghotbi R, Bertilsson L, Jankovic S, Aklillu E. Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes. Eur J Clin Pharmacol. 2008;64:381–385. [PubMed]
23. Djordjevic N, Ghotbi R, Jankovic S, Aklillu E. Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 −163C > A polymorphism. Eur J Clin Pharmacol. 2010;66:697–703. [PubMed]
24. Ingelman-Sundberg M, Sim SC, Nebert DW. Coffee, myocardial infarction, and CYP nomenclature. JAMA. 2006;296:764–765. [PubMed]
25. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA. 2006;295:1135–1141. [PubMed]
26. Han XM, Ouyang DS, Chen XP, Shu Y, Jiang CH, Tan ZR, et al. Inducibility of CYP1A2 by omeprazole in vivo related to the genetic polymorphism of CYP1A2. Br J Clin Pharmacol. 2002;54:540–543. [PMC free article] [PubMed]
27. Obase Y, Shimoda T, Kawano T, Saeki S, Tomari SY, Mitsuta-Izaki K, et al. Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma. Clin Pharmacol Ther. 2003;73:468–474. [PubMed]
28. Aklillu E, Carrillo JA, Makonnen E, Hellman K, Pitarque M, Bertilsson L, 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;64:659–669. [PubMed]
29. Takata K, Saruwatari J, Nakada N, Nakagawa M, Fukuda K, Tanaka F, et al. Phenotype-genotype analysis of CYP1A2 in Japanese patients receiving oral theophylline therapy. Eur J Clin Pharmacol. 2006;62:23–28. [PubMed]
30. Sachse C, Brockmoller J, Bauer S, Roots I. Functional significance of a C– >A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol. 1999;47:445–449. [PMC free article] [PubMed]
31. Nordmark A, Lundgren S, Ask B, Granath F, Rane A. The effect of the CYP1A2 *1F mutation on CYP1A2 inducibility in pregnant women. Br J Clin Pharmacol. 2002;54:504–510. [PMC free article] [PubMed]
32. El-Sohemy A, Cornelis MC, Kabagambe EK, Campos H. Coffee, CYP1A2 genotype and risk of myocardial infarction. Genes Nutr. 2007;2:155–156. [PMC free article] [PubMed]
33. Popat RA, Van Den Eeden SK, Tanner CM, Kamel F, Umbach DM, Marder K, et al. Coffee, ADORA2A, and CYP1A2: the caffeine connection in Parkinson’s disease. Eur J Neurol. 2011;18:756–765. [PMC free article] [PubMed]
34. Tan EK, Chua E, Fook-Chong SM, Teo YY, Yuen Y, Tan L, et al. Association between caffeine intake and risk of Parkinson’s disease among fast and slow metabolizers. Pharmacogenet Genomics. 2007;17:1001–1005. [PubMed]
35. Facheris MF, Schneider NK, Lesnick TG, de Andrade M, Cunningham JM, Rocca WA, et al. Coffee, caffeine-related genes, and Parkinson’s disease: a case-control study. Mov Disord. 2008;23:2033–2040. [PubMed]
36. Laika B, Leucht S, Heres S, Schneider H, Steimer W. Pharmacogenetics and olanzapine treatment: CYP1A2*1F and serotonergic polymorphisms influence therapeutic outcome. Pharmacogenomics J. 2010;10:20–29. [PubMed]
37. Basile VS, Ozdemir V, Masellis M, Walker ML, Meltzer HY, Lieberman JA, et al. A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia. Mol Psychiatry. 2000;5:410–417. [PubMed]
38. Bakker PR, van Harten PN, van Os J. Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2 and MnSOD genes: a meta-analysis of pharmacogenetic interactions. Mol Psychiatry. 2008;13:544–556. [PubMed]
39. Boke O, Gunes S, Kara N, Aker S, Sahin AR, Basar Y, et al. Association of serotonin 2A receptor and lack of association of CYP1A2 gene polymorphism with tardive dyskinesia in a Turkish population. DNA Cell Biol. 2007;26:527–531. [PubMed]
40. Fu Y, Fan CH, Deng HH, Hu SH, Lv DP, Li LH, et al. Association of CYP2D6 and CYP1A2 gene polymorphism with tardive dyskinesia in Chinese schizophrenic patients. Acta Pharmacol Sin. 2006;27:328–332. [PubMed]
41. Tiwari AK, Deshpande SN, Rao AR, Bhatia T, Mukit SR, Shriharsh V, et al. Genetic susceptibility to tardive dyskinesia in chronic schizophrenia subjects: I. Association of CYP1A2 gene polymorphism. Pharmacogenomics J. 2005;5:60–69. [PubMed]
42. Schulze TG, Schumacher J, Muller DJ, Krauss H, Alfter D, Maroldt A, et al. Lack of association between a functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene and tardive dyskinesia in schizophrenia. Am J Med Genet. 2001;105:498–501. [PubMed]
43. Tay JK, Tan CH, Chong SA, Tan EC. Functional polymorphisms of the cytochrome P450 1A2 (CYP1A2) gene and prolonged QTc interval in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:1297–1302. [PubMed]
44. Lin KM, Tsou HH, Tsai IJ, Hsiao MC, Hsiao CF, Liu CY, et al. CYP1A2 genetic polymorphisms are associated with treatment response to the antidepressant paroxetine. Pharmacogenomics. 2010;11:1535–1543. [PubMed]
45. Hamdy SI, Hiratsuka M, Narahara K, Endo N, El-Enany M, Moursi N, et al. Genotyping of four genetic polymorphisms in the CYP1A2 gene in the Egyptian population. Br J Clin Pharmacol. 2003;55:321–324. [PMC free article] [PubMed]
46. Sachse C, Bhambra U, Smith G, Lightfoot TJ, Barrett JH, Scollay J, 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. [PMC free article] [PubMed]
47. Nakajima M, Yokoi T, Mizutani M, Kinoshita M, Funayama M, Kamataki T. Genetic polymorphism in the 5′-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans. J Biochem. 1999;125:803–808. [PubMed]
48. Matsumoto C, Ohmori O, Shinkai T, Hori H, Nakamura J. Genetic association analysis of functional polymorphisms in the cytochrome P450 1A2 (CYP1A2) gene with tardive dyskinesia in Japanese patients with schizophrenia. Psychiatr Genet. 2004;14:209–213. [PubMed]
49. Soyama A, Saito Y, Hanioka N, Maekawa K, Komamura K, Kamakura S, et al. Single nucleotide polymorphisms and haplotypes of CYP1A2 in a Japanese population. Drug Metab Pharmacokinet. 2005;20:24–33. [PubMed]
50. Ghotbi R, Gomez A, Milani L, Tybring G, Syvanen AC, Bertilsson L, et al. Allele-specific expression and gene methylation in the control of CYP1A2 mRNA level in human livers. Pharmacogenomics J. 2009;9:208–217. [PubMed]