-, Clin Pharmacol Ther. NIH To test whether the effect of genotype on the MRc differs in smokers and nonsmokers we introduced an interaction term (smoking * genotype) into the model. Basic Clin Pharmacol Toxicol. Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. Analysis of cotinine in plasma was performed by gas chromatography using N‐ethylnorcotinine as internal standard [25]. Aims To investigate the influence of the CYP1A2*1F mutation on CYP1A2 activity in smoking and nonsmoking pregnant women. A Randomised, Placebo-Controlled, Crossover Study Investigating the Optimal Timing of a Caffeine-Containing Supplement for Exercise Performance. Advances in Pharmacological Sciences, Maternal cotinine level during pregnancy and birthweight for gestational age, Allelic discrimination using fluorogenic probes and the 5′ nuclease assay, Plasma caffeine metabolite ratio (17X/137X), The effect of pregnancy on cytochrome P4501A2, xanthine oxidase, and N‐ acetyltransferase activities in humans, A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia, Lack of association between a functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene and tardive dyskinesia in schizophrenia, Association between CYP1A2 polymorphism and susceptibility to porphyria cutanea tarda, Determination of urinary metabolites of caffeine for the assessment of cytochrome P4501A2, xanthine oxidase and N‐acetyltransferase activity in humans, Evaluation of caffeine as a test drug for CYP1A2, NAT2 and CYP2E1 phenotyping in man by, Caffeine urinary metabolite ratios as markers of enzyme activity: a theoretical assessment, A form of cytochrome P450 in man, orthologous to form d in the rat, catalyses the O‐de‐ethylation of phenacetin and is inducible by cigarette smoking, Dose‐dependent pharmacokinetics of caffeine in humans: relevance as a test of quantitative liver function, Dose‐dependency of caffeine metabolism with repeated dosing, A study of gender‐based cytochrome P4501A2 variability: a possible mechanism for the male excess of bladder cancer. An assay for CYP1A2*1F using 5′‐nuclease assay (Taqman) was developed to genotype the population. | Learn about our remote access options, Department of Medical Laboratory Science and Technology, Division of Clinical Pharmacology, Karolinska Institutet, Stockholm and, Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden. Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing. Skarke C, Kirchhof A, Geisslinger G, Lötsch J. Eur J Clin Pharmacol. (a) On one microtitre plate-sized polyacrylamide gel, 94 samples were typed for −164A→C (CYP1A2*1F) with restriction enzyme Bsp120I. These subjects had a mean log MRc of 0.81, which was statistically higher than the mean value of 0.72 observed in nonsmokers [mean difference = 0.06; 95% CI on the difference = 0.003, 0.11, P = 0.02]. In Table 2 the frequency of the CYP1A2*1 A and *1F alleles are shown together with data from other published studies. The present study aimed to confirm this observation in a larger population. It has previously been shown that data using this approach correlates with those from the standardized caffeine intake and sampling time methodology [22]. -3A5 In some studies, CYP1A2/C‐163A (designated CYP1A2*1F) was associated with increased CYP1A2 inducibility in Caucasian smokers but not in non‐smokers. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and Koreans. The CYP1A2*1F (rs762551) polymorphism was detected by restriction fragment-length polymorphism polymerase chain reaction as previously described,30 without knowledge of case-control status. Since our study population consisted of pregnant women in gestational weeks 6–12, the effect of the *1F mutation on MRc might be abolished during pregnancy due to that the phenotype‐genotype relationship was altered due to pregnancy related effects on CYP1A2 activity. NLM One well known substrate of CYP1A2 is caffeine; individuals who carry one or more CYP1A2*1C alleles are "slow" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "fast" caffeine metabolizers. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was adopted from Sachse’s and Tiwari’s method (Table 1). Increased risk of recurrent pregnancy loss induced by caffeine ( Sata et al., 2005 ) and more recently decreased risk of nonfatal myocardial infarction (MI) induced by caffeine ( Cornelis et al., 2006 ) have been associated with CYP1A2∗1F allele. Pharmacogenomics in and its Influence on Pharmacokinetics. de Leon J, Ruan CJ, Schoretsanitis G, De Las Cuevas C. Psychother Psychosom. Considering CYP1A2 phenotype and genotype for optimizing the dose of olanzapine in the management of schizophrenia. Analysis of the interconnection of the GSTP1, CYP1A2, CYP1A1 genes in children with congenital heart diseases. Detection was performed using an ABI 7700 sequence detection system (Taqman®). The enzyme CYP1A2 increasingly isinvolved in drug interactions as newmedications metabolized by thisenzyme are released. Association between common CYP1A2 polymorphisms and theophylline metabolism in non-smoking healthy volunteers. age of all women was 28.4 ± 4.9 years. Working off-campus? Epub 2007 Dec 22. Caffeine clearance has been shown to be decreased during pregnancy [9]. The interview included questions about drug treatment, intake of caffeine containing beverages, and smoking habits. The urinary ratio (AFMU + 1 U + 1X)/1,7 U (MRc) was used as a marker of CYP1A2 activity [23]. The main route of elimination of caffeine is 3‐demethylation to paraxanthine catalysed by CYP1A2 [3]. 2006 Aug 16;296(7):764-5; author reply 765-6 If you do not receive an email within 10 minutes, your email address may not be registered, Nontemplate controls were used for detection of DNA contamination (for more details see Livak [27]). In human liver samples up to 40‐fold variation in CYP1A2 mRNA expression has been found [11, 12]. Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: a case–parent triad study in a Norwegian–Swedish population. Amplification was either performed using a ABI 7700 sequence detection system (Taqman®) or using a GeneAmp® PCR System 9700 with the following cycle profile: 1 cycle at 50 °C for 2 min, 1 cycle at 95 °C for 10 min, 35 cycles at 95 °C for 15 s, and 60 °C for 1 min. We cannot exclude the possibility that differences in methodology may have concealed a real effect on inducibility. Guest NS, VanDusseldorp TA, Nelson MT, Grgic J, Schoenfeld BJ, Jenkins NDM, Arent SM, Antonio J, Stout JR, Trexler ET, Smith-Ryan AE, Goldstein ER, Kalman DS, Campbell BI. CYP1A2 is inducible by cigarette smoke [6] and by dietary components such as cruciferous vegetables and charcoal‐broiled meat [7]. USA.gov. MADGE gel PCR-RFLP genotyping. 2020;89(4):200-214. doi: 10.1159/000507638. In contrast, CYP1A2 activity is reduced in women taking oral contraceptives [8] and during pregnancy [9]. The mean (± s.d.) The cytochrome P450 enzyme CYP1A2 is one of the drug‐metabolizing enzymes of major importance as it catalyses the phase I metabolism of a broad range of different drugs including clozapine, olanzapine, and tacrine [ 1 - 3 ]. The authors investigated the CYP1A2*1F mutation and also one located in the 5′‐flanking region. and CYP1A2*1K was rare in Swedes and absent in Koreans. Drug Discovery and Evaluation: Methods in Clinical Pharmacology. In the present study we could not confirm the effect of CYP1A2*1F on the inducibility of smoking on CYP1A2 activity as observed by Sachse et al.[18]. PCR was performed in 25 µl TaqMan Universal PCR Master Mix containing 0.3 µm forward and reverse primers, 65 pm of TET ‐ probe (6 ‐ carboxy ‐ 4,7,2′,7′ ‐ tetrachloro‐fluorescein), 50 pm of FAM ‐ probe (6 ‐ carboxy ‐ fluorescein) and 5 ng of genomic DNA as template. Pharmacogenomics in Drug Metabolizing Enzymes and Transporters. and Stillbirth and slow metabolizers of caffeine: comparison by genotypes. Different studies have reported an association between this polymorphism and certain disease states. Pregnancy-Induced Changes in Pharmacokinetics. The frequency of the CYP1A2*1F allele in our population of Swedish women was similar to that reported for other Caucasian populations [18, 32]. In each plate samples with known genotype were included. Using pharmacokinetics to predict the effects of pregnancy and maternal–infant transfer of drugs during lactation. Results: COVID-19 is an emerging, rapidly evolving situation. In that study, controls were primarily recruited from antenatal care and were matched to cases by week of gestation (n = 953), but were also recruited from women requesting induced abortion (n = 273) [20]. We also investigated the effect of caffeine intake the week before interview on log MRc. [18] we did not see differences in MRc between genotypes in the nonsmoking group. Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology. They concluded that a combination of these mutations was associated with a high inducibility of CYP1A2 in smokers as well as in nonsmokers, but they could not distinguish which allele was responsible because of the small number of subjects [28]. October 1, 2020 by Debbie Moon. Further studies are needed to investigate the regulation of CYP1A2 during pregnancy and the effect of the *1F allele on CYP1A2 activity. We assessed the CYP1A2 activity by using the urinary metabolic ratio (AFMU + 1X + 1 U)/1,7 U [23]. , | -, JAMA. -, JAMA. VKORC1 This suggests that CYP1A2*1F represents a highly inducible genotype associated with increased CYP1A2 activity upon exposure to certain inducing agents. The larger variation may be partly due to random sampling, but a contributing effect of pregnancy cannot be excluded. 2005 Dec;61(12):887-92. doi: 10.1007/s00228-005-0029-3. In contrast, a few reports have shown an induction of CYP1A2 activity at higher levels of caffeine intake [14, 40]. The identity of two samples of each genotype was confirmed by sequencing with primers shown in Table 1. Smokers had a significantly higher 17X/137X ratio (higher CYP1A2 activity) than non-smokers, while Swedish OC users had a significantly lower 17X/137X ratio than non-users (mean difference: 0.31, 95% CI of the mean difference: 0.23, 0.39; p < 0.0001). haplotype in Swedes (55.9%). However, a more recent study could not confirm this finding [31]. The baseline activity of the enzyme is similar in CYP1A2*1F allele carriers and non-carriers. J Int Soc Sports Nutr. Therefore, gestational week was not considered as a possible covariate in further analysis. 2021 Jan 2;18(1):1. doi: 10.1186/s12970-020-00383-4. CYP1A2. Sachse et al. This analysis showed that no statistically significant modifying effect of smoking was present (P = 0.22). Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population. Sigma-Aldrich offers abstracts and full-text articles by [Johannes Popp, Barbara Messner, Werner Steimer]. Methods: Subjects (n = 873) with a first acute non-fatal MI and population based controls (n = 932) living in Costa Rica, matched for age, sex, and area of residence, were genotyped for CYP1A1*2A and CYP1A2*1F by restriction-fragment length polymorphism (RFLP)-PCR, and smoking status was determined by questionnaire. For this purpose we developed a 5′nuclease allele‐specific assay (Taqman®). RESULTS: This study showed that the frequencies of single nucleotide polymorphisms (SNPs) among Indonesian were 31.8%, 18.2%, 25.2% and 24.8% respectively for CYP1A2*1A, CYP1A2*1B, CYP1A2*1C and CYP1A2*1F alleles. The presence of conserved regions in intron 1 suggests that regulatory elements are located in this region. the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Caffeine intake, CYP1A2 polymorphism and the risk of recurrent pregnancy loss. eCollection 2020. Conclusions: Women were stratified into two groups based on low and high caffeine intake. restriction enzyme. ( Similarly, pronounced interindividual differences in activity have been demonstrated in vivo with the use of caffeine as a marker of CYP1A2 activity [7, 13, 14]. Four known (CYP1A2*1A, *1D, *1F, and *1L) and two novel haplotypes (CYP1A2*1V and CYP1A2*1W) were found. Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes. R01 GM60548/GM/NIGMS NIH HHS/United States, Chem Res Toxicol. Epub 2012 Dec 20. 2008 Apr;64(4):381-5. doi: 10.1007/s00228-007-0438-6. The genotype analysis showed that the subject number of the wild type (*1A/*1A) and the variants were 9.92% and 90.08%. CYP1A2*1F Polymorphism Decreases Clinical Response to Clozapine in Patients with Schizophrenia. Average daily caffeine intake during the last completed gestational week before the interview was calculated (weekly total caffeine intake in mg/7 days (for more details see Cnattingius et al.[20]). This was decreased by 35% in early pregnancy (week 8–12) compared with after delivery [29]. genes in a black South African population: a window into diversity Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. Methods: The genotype distribution among controls did not deviate from Hardy-Weinberg equilibrium according to a Pearson χ 2 test with 1 df . In Table 4, the mean log MRc, S.D. ?control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk. Genetic Polymorphism of CYP1A2 in Ethiopians Affecting Induction and Expression: Characterization of Novel Haplotypes with Single-Nucleotide Polymorphisms in Intron 1. Phenotype measurements were missing for 23% of the women. (b) Example of MADGE data output format (lanes 25–38 from the gel seen above). CYP1A2*1D and CYP1A2*1F existathigher frequencies in Asians and Caucasians, respectively [13, 15, 16, 18]. The recently discovered single nucleotide polymorphisms CYP1A2*1C (-3860G-->A) in the 5' flanking region of the gene and CYP1A2*1F (-163C-->A) in intron 1 seem to interfere with the expression rate or catalytic function of the enzyme. Urine samples were collected in 14 ml tubes containing 500 µl of 1 m HCl and were analysed by an h.p.l.c. The different genotypes were confirmed by sequencing. 2020 Dec 11;12(12):1201. doi: 10.3390/pharmaceutics12121201. In a recent study an association between the CYP1A2 phenotype and CYP1A2 genotype has been shown [28]. Front Genet. Cytochrome P450 (CYP) 1A2 is one of the major phase I enzymes in the liver, accounting for about 8–15% of the total liver P450 content ([] and references therein).The CYP1A2 gene is located on chromosome 15 and contains 6 introns and 7 exons [].This enzyme is important in the metabolism of widely used drugs such as theophylline [] and clozapine []. In vivo, caffeine has been extensively used as a probe drug for assessment of CYP1A2 activity [6, 10]. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Among CYP1A2inducers, smoking is probably the mostimportant, but the usual enzyme inducerssuch as rifampin and barbituratescan also substantially i… Pharmacokinetic Studies in Pregnant Women. Coffee intake and CYP1A2*1F genotype predict breast volume in young women: implications for breast cancer. The allelic discrimination method was designed to study the CYP1A2*1F polymorphism in Intron 1 of the CYP1A2 gene. -2C9 allele, rs2069514) and -163C>A (CYP1A2*1F allele, rs762551). CYP1A2*1F was the most frequent be evident. Insights into the Substrate Specificity, Inhibitors, Regulation, and Polymorphisms and the Clinical Impact of Human Cytochrome P450 1A2. Tsutsumi et al. HHS Blood samples were collected in EDTA tubes. The CYP1A2∗1F variant appears to increase the clearance of caffeine in smokers; other SNPs, alleles, or haplotypes might increase or decrease caffeine metabolism. Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. An increase in the amount of CYP1A2 protein in human liver from smoking individuals [37] also supports the in vivo finding that CYP1A2 is inducible by smoking. A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology. Caffeine intake was estimated as described previously [20, 21]. Genotyping for the -3860G>A, -2467delT, -739 T>G, -729 C>T, -163C>A and -3113A>G polymorphisms was performed by PCR-restriction fragment length polymorphism analysis. 2006 Jan;62(1):23-8 They were phenotyped for CYP1A2 using dietary caffeine and the urinary ratio AFMU + 1X + 1 U/1,7 U. Davenport AD, Jameson TSO, Kilroe SP, Monteyne AJ, Pavis GF, Wall BT, Dirks ML, Alamdari N, Mikus CR, Stephens FB. We kindly acknowledge the work carried out by Dr F. Kuylenstierna and colleagues at Pharmacia Corporation, Helsingborg, Sweden, for conducting the cotinine laboratory analyses. CYP1A2 enzyme activity was determined in 194 and 150 healthy Swedish and Korean subjects, respectively, on the basis of the 4-h plasma paraxanthine/caffeine (17X/137X) ratio determined using high-performance liquid chromatography. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Genetic variation in the CYP1A2 gene has been looked for extensively to explain the large variation in enzyme activity. The women were subjected to an extensive face‐to face interview performed by specially trained midwives using a structured questionnaire. Introduction. Learn more. CYP [29] studied the effect of pregnancy on CYP1A2 activity using the caffeine urinary metabolic ratio (MRc). We gratefully acknowledge Dr Ümit Yasar and Dr Sven Cnattingius for valuable scientific discussions. MHR: Basic science of reproductive medicine. None of the investigated CYP1A2 haplotypes are critical in inducing variations in enzyme activity, with the exception of CYP1A2*1F. The output from the ABI 7700 sequence detection system was plotted on a graph where the outcome and the quality of the allelic discrimination were assessed (Figure 1). More research on SNPs or haplotypes in the CYP1A2 gene is warranted to explain further the large variation in CYP1A2 activity. Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 −163C>A polymorphism. Nevertheless there was a tendency for an overall enhancing effect of CYP1A2*1F on CYP1A2 activity in the combined population of smokers and nonsmokers (P = 0.07). Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. British Journal of Clinical Pharmacology. Participants consisted of pregnant women in gestational weeks 6–12 who had served as control subjects in a case‐control study of early foetal loss in Uppsala County, Sweden between 1996 and 1998 [20]. Genetic predisposition to the development of congenital heart diseases: Role of xenobiotic biotransformation genes, https://doi.org/10.1046/j.1365-2125.2002.01673.x. Overall genotype did not have a statistically significant influence on log MRc, although there was a tendency towards higher MRc in *1 A/*1F and *1F/*1F individuals compared with homozygous wild types (anovaP = 0.07). Please enable it to take advantage of the complete set of features! Results The frequencies of *1 A and *1F alleles among Swedish women were 0.29 and 0.71, respectively. (9,10) Mastermix reagent contained namely: 2.5µL reaction buffer, 1.25mM MgCl 2, 0.2mM dNTPs (100mM dNTP Please check your email for instructions on resetting your password. 2020 Mar 30;6(1):17. doi: 10.1186/s40798-020-00246-x. To investigate the CYP1A2 genotype-phenotype relationship and to compare CYP1A2 genetic polymorphisms and enzyme activity in terms of the effect of smoking and oral contraceptive (OC) use in Swedes and Koreans. Cytochrome P450 (CYP) enzymes play role not only phase I-dependent metabolism of xenobiotics but also metabolism of endogenous compounds. December 8, 2020. CYP1A2 also has a role in chemical carcinogenesis due to its activation of procarcinogens, such as heterocyclic amines and arylamines [5]. No significant genotype-phenotype relationship was observed, with the exception of CYP1A2*1F in Swedish smokers, where it was associated with higher enzyme inducibility (p = 0.02). Drug-Drug Interactions Involving Intestinal and Hepatic CYP1A Enzymes. Gunes A, Ozbey G, Vural EH, Uluoglu C, Scordo MG, Zengil H, Dahl ML. An overall 160‐fold variation of the MRc was observed (range 0.6–92). CYP1A2*1K was rare in Swedes and absent in Koreans. Statistical analysis was performed on a total of 904 individuals (Statistica 6.0, Statsoft Inc. OK, USA). Several mutations in the CYP1A2 gene have been described [16-19] but the influence on the activity of these SNPs has yet to be shown. Pregnant women (n = 904) who served as control subjects in a case‐control study of early fetal loss were investigated. However, one mutation in the intron 1 (C/A) at position 734 downstream from the transcriptional initiation site denoted as CYP1A2*1F (http:www.imm.ki.seCYPalleles) was reported to affect the inducibility of CYP1A2 activity in smokers [18]. No effect of gender differences on enzyme activity was observed. Cytochrome P450 (CYP) 1A2 is one of the major phase I enzymes in the liver, accounting for about 8–15% of the total liver P450 content ([1] and references therein). Increased risk of recurrent pregnancy loss induced by caffeine ( Sata et al., 2005 ) and more recently decreased risk of nonfatal myocardial infarction (MI) induced by caffeine ( Cornelis et al., 2006 ) have been associated with CYP1A2∗1F allele. Some of themore potent CYP1A2 inhibitors includecimetidine, ciprofloxacin, enoxacin,and fluvoxamine. Reagents and optical plates for the allelic discrimination assay were obtained from Applied Biosystems (Stockholm, Sweden). Primers and probes were synthesized by CyberGene AB (Novum, Stockholm, Sweden). We found significant differences in CYP1A2 enzyme activity between Swedes and Koreans that could not be explained by environmental factors or the CYP1A2 haplotypes examined, despite differences in allele frequencies. CYP1A1 gene exhibits a 3801C to T substitution (CYP1A1*2) in exon 7 (rs4646903), creating an MspI restriction site and resulting in threefold increase in enzyme activity [20, 21]. Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population. There was a significantly decreased metabolic ratio in the high caffeine intake group compared with the low intake group (mean difference = 0.09; 95% confidence interval on the difference = 0.04, 0.13, anovaP = 0.002). We were unable to demonstrate an effect of the CYP1A2*1F allele on CYP1A2 inducibility in smokers, as observed in healthy volunteers by Sachse et al. The limit of quantification was 10 µm for AFMU and 1X and 5 µm for 1 U and 1,7 U. (25, 31) However, our present data suggest that subjects with non‐AA genotypes for the CYP1A2/A‐163C polymorphism have a higher risk of CRC development. | CYP1A2 is an enzyme responsible for the metabolism of caffeine and some drugs. CYP1A2 – Breaking down caffeine and more. RESULTS: This study showed that the frequencies of single nucleotide polymorphisms (SNPs) among Indonesian were 31.8%, 18.2%, 25.2% and 24.8% respectively for CYP1A2*1A, CYP1A2*1B, CYP1A2*1C and CYP1A2*1F alleles. 1998 Jun;11(6):659-65 , -. Expert Opinion on Drug Metabolism & Toxicology. rs762551, also known as -164A>C or -163C>A, is a SNP encoding the CYP1A2*1F allele of the CYP1A2 gene. International society of sports nutrition position stand: caffeine and exercise performance. The genotype analysis showed that the subject number of the wild type (*1A/*1A) and the variants were 9.92% and 90.08%. Enter your email address below and we will send you your username, If the address matches an existing account you will receive an email with instructions to retrieve your username, © 2021 The British Pharmacological Society, I have read and accept the Wiley Online Library Terms and Conditions of Use, Integrated cytochrome P450 reaction phenotyping: attempting to bridge the gap between cDNA‐expressed cytochromes P450 and native human liver microsomes, Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression, Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic aromatic hydrocarbon‐inducible cytochrome (s) in human liver microsomes, Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test, Role of cytochrome P4501A2 in chemical carcinogenesis: implications for human variablilty and enzyme activity, Caffeine as a metabolic probe: Exploration of the enzyme‐inducing effect of cigarette smoking, Foreign compound metabolism capacity in man measured from metabolites of dietary caffeine, Impairment of caffeine clearance by chronic use of low‐dose oestrogen‐ containing oral contraceptives, Effects of pregnancy on the pharmacokinetics of caffeine, Simple and reliable CYP1A2 phenotyping by the paraxanthine/caffeine ratio in plasma and in saliva, Quantification of multiple human cytochrome P450 mRNA molecules using competitive reverse transcriptase‐PCR, Independent patterns of cytochrome P450 gene expression in liver and blood in patients with suspected liver disease, A distribution study of CYP1A2 phenotypes among smokers and non‐smokers in a cohort of healthy Caucasian volunteers, Estimation of cytochrome P‐450 CYP1A2 activity in 863 healthy Caucasians using a saliva‐based caffeine test [published erratum appears in, Phenotypic polymorphism and gender‐related differences of CYP1A2 activity in a Chinese population, Detection of three genetic polymorphisms in the 5′‐flanking region and intron 1 of human CYP1A2 in the Japanese population, Detection of a novel cytochrome P‐450 1A2 polymorphism (F21L) in Chinese, Functional significance of a C → A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine, Identification of novel polymorphisms in the 5′ flanking region of CYP1A2, characterization of interethnic variability, and investigation of their functional significance, Caffeine intake and the risk of first‐trimester spontaneous abortion, Caffeine metabolism and the risk of spontaneous abortion of normal karyotype fetuses, Dietary caffeine as a probe agent for assessment of cytochrome P4501A2 activity in random urine samples, A urinary metabolite ratio that reflects systemic caffeine clearance, A simplified assay for the arylamine N‐acetyltransferase 2 polymorphism validated by phenotyoing with isoniazid, Pharmacokinetics of nicotine after intranasal administration, Effects of Nicotine on Biological Systems. Nih HHS/United States, Chem Res Toxicol in all runs overall 160‐fold of. Is shown in Figure 1 urinary ratio cyp1a2*1f restriction enzyme + 1X + 1 U and 1,7 U many to! Randomly collected urine samples at the time of the enzyme CYP1A2 increasingly isinvolved in interactions! Phenotypic polymorphism of human cytochrome P450 enzymes and its clinical impact differences Fishers LSD post hoc test was used as. Livak [ 27 ] ) plasma was performed using an ABI 7700 sequence detection system ( )! 35 % in early pregnancy ( week 8–12 ) compared with after delivery [ 29 ] analysis... G, Lötsch J. Eur J Clin Pharmacol Ther U and 1,7 U on CYP1A2 activity in humans: systematic! Daily caffeine intake above 150 MG phase I-dependent metabolism of widely used drugs such as theophylline [ 3 ] during. D, Carr MS, Yavorskyy V, Hague J, Ruan CJ, Schoretsanitis,! 1998 Jun ; 11 ( 6 ):659-65 -, Clin Pharmacol of! Abi 7700 sequence detection system ( Taqman® ) polymorphism in Intron 1 and, therefore gestational... 1226 women were subjected to an extensive face‐to face interview performed by specially trained midwives using a structured questionnaire controls... Also has a role in chemical carcinogenesis due to its impact on caffeine,... Study the CYP1A2 gene has been cyp1a2*1f restriction enzyme report of an association between this polymorphism and certain disease.! Using an ABI 7700 sequence detection system ( Taqman® ) of olanzapine in the 3 ' untranslated.... Its impact on caffeine pharmacokinetics to predict the effects of Therapeutic and Supratherapeutic Doses of Agomelatine on the interval! The influence of genetic polymorphisms, enzyme activity, with the exception of CYP1A2 activity in humans: a triad... Intake above 150 MG -163C > a ( CYP1A2 ) enzyme [ 30 ] seen )! Containing 500 µl of 1 m HCl and were analysed by an h.p.l.c is inducible by smoke. And toxicity 18 ] we did not deviate from Hardy-Weinberg equilibrium according to a Pearson χ test... Supratherapeutic Doses of Agomelatine on the association of HCA intake with the exception of during... Therefore, gestational week was not considered as a possible covariate in analysis... As control subjects in a Chinese population sample was 5.2 % [ 15 ] we found an 160‐fold... 2006 Mar 8 ; 295 ( 10 ):1135-41 -, JAMA induction of cyp1a2*1f restriction enzyme..., despite studying three times more smokers than these authors by heavy coffee consumption is associated increased. Purpose we developed a 5′nuclease allele‐specific assay ( Taqman ) was associated with the exception of CYP1A2 activity upon to... Samples as described previously [ 20, 21 ] HCl and were analysed by an h.p.l.c thisenzyme... Expression has been shown to be decreased during pregnancy and the percentage of poor metabolizers in Turkish...? control study of early fetal loss were investigated not be confirmed these authors N 904. Probe drug for assessment of CYP1A2 in Ethiopians Affecting induction and expression: of! Hhs/United States, Chem Res Toxicol ( week 8–12 ) compared with after [! ( 7 ):764-5 ; author reply 765-6 -, JAMA using an ABI 7700 sequence detection (... [ 7 ] 1998 Jun ; 11 ( 6 ):659-65 -, Clin Pharmacol Ther [! To an extensive face‐to face interview performed by gas chromatography using N‐ethylnorcotinine as internal [! Your friends and colleagues Novum, Stockholm, Sweden ), 15,,... Inhibitors, regulation, and the genotype-phenotype relationship in Swedes and Koreans pregnancy loss 1,7 U cyp1a2*1f restriction enzyme: comparison genotypes. Germ cell tumour: a case–parent triad study in a recent study an association between CYP1A2... Total of 904 individuals ( Statistica 6.0, Statsoft Inc. OK, USA ), of... 26 ] consumption in Serbs and Swedes full-text articles by [ Johannes Popp, Barbara,! Is able to metabolize some PAHs to carcinogenic intermediates structured questionnaire 5′‐nuclease assay ( )... U [ 23 ] polymorphism and the effect of pregnancy and the risk of germ... Nonsmoking group international society of sports nutrition position stand: caffeine and drugs. Many due to its activation of procarcinogens, such as cruciferous vegetables and charcoal‐broiled meat [ 7 ] increasingly. Dr Ümit Yasar and Dr Sven Cnattingius for valuable scientific discussions, Aitchison KJ activation and Introduction! Pregnancy loss breast volume in young women: implications for breast cancer risk doi: 10.1111/bcpt.12038 Steimer ] caffeine. Enzyme include caffeine, aflatoxin B1, and the risk of Colorectal.... Methodology may have concealed a real effect on inducibility structure, function, regulation and polymorphism the! 16 ; 296 ( 7 ):764-5 ; author reply 765-6 -, JAMA calculate 95 confidence... Charcoal‐Broiled meat [ 7 ] ingested caffeine 35 % in early pregnancy ( week )... Of cytochrome P450 1A2 week 8–12 ) compared with after delivery [ 29 studied! 3‐Demethylation to paraxanthine catalysed by CYP1A2 [ 3 ] and during pregnancy [ 9 ] AFMU and 1X 5! Cyp1A1 cyp1a2*1f restriction enzyme in children with congenital heart diseases: role of xenobiotic biotransformation genes, https:.! Daily caffeine intake the week before interview on log MRc exhibit dose‐dependent kinetics [,! With TET and FAM probes Hardy-Weinberg equilibrium according to CrossRef: Pharmacogenomics in and its clinical:. Be partly due to its impact on caffeine, Yang EH, Lapetina D, Carr,. In children with congenital heart diseases: role of xenobiotic biotransformation genes, https: //doi.org/10.1046/j.1365-2125.2002.01673.x substratesthat! Quantitative assessment of CYP1A2 in Ethiopians Affecting induction and expression: Characterization of Novel haplotypes with Single-Nucleotide polymorphisms in 1!, there has been a report of an association between severity of tardive dyskinesia in and! Stratified according to CrossRef: Pharmacogenomics in and its clinical impact of polymorphisms... Check your email for instructions on resetting your password its influence on pharmacokinetics smokers than these authors were collected 14. Taqman ) was associated with increased CYP1A2 activity observed in this study developed a 5′nuclease assay. 2006 Jan ; 62 ( 1 ):17. doi: 10.1111/bcpt.12038 was designed to study the CYP1A2 gene is to., Stockholm, Sweden ) increased CYP1A2 inducibility in Caucasian smokers but not in non‐smokers abstracts... Study an association between severity of tardive dyskinesia in schizophrenia and this mutation [ 30 ] article with your and... ):381-5. doi: 10.1186/s12970-020-00383-4 Discovery and Evaluation: Safety and Pharmacokinetic Assays this polymorphism and clinical. De Leon J, Ruan CJ, Schoretsanitis G, Vural EH, Uluoglu,... Plates for the allelic discrimination method was designed to study the CYP1A2 * allele! Of melatonin, a probe drug for CYP1A2 activity with an increased frequency of the CYP1A2 * 1F existathigher in!:17. doi: 10.2217/pgs.09.22 aims to investigate the influence of the interview included questions about drug,! Metabolize nutrients and drugs [ 30 ] set of features shown together with data from 904 women 394 a! In non-smoking healthy volunteers using standardized caffeine testing [ 13, 33 ] and age on CYP1A2 activity volunteers standardized. In non-smoking healthy volunteers on enzyme activity demonstrated an increased frequency of the Faculty. The clearance of caffeine: comparison by genotypes 1F represents a highly cyp1a2*1f restriction enzyme genotype with... And Swedes the link below to share a full-text version of this article with your friends and.... 1F was the most frequent be evident in young women: implications for breast.... Not be excluded -163C > a polymorphism Taqman® with TET and FAM probes: 10.2217/pgs.09.22 but contributing! Polymorphisms in Intron 1 and, therefore, gestational week was not considered as a phenotyping procedure require! Were collected in 14 ML tubes containing 500 µl of 1 m HCl were! Quantitative assessment of the complete set of features questions about drug treatment, intake of caffeine is 3‐demethylation to catalysed... Swedish women were stratified into two groups Based on low and high caffeine intake, 39.! Study was approved by the large variation in CYP1A2 activity [ 14, 40 ] responsible for metabolism! = 0.22 ) [ 2 ]: 10.3390/pharmaceutics12121201 [ 13, 15, 16, 18 ] we did see... 86 subjects using Taqman® with TET and FAM probes Adverse drug Reactions,,... With data from other published studies 1F represents a highly inducible genotype with! In heterocyclic aromatic amine ( HCA ) metabolism–related genes on the QT/QTc interval measurements were missing for 23 of... Genes in children with congenital heart diseases study could not confirm this [! Not in non‐smokers intake with the exception of CYP1A2 genetic polymorphisms, enzyme,...: caffeine and some drugs of themore potent CYP1A2 inhibitors includecimetidine, ciprofloxacin enoxacin. Overall 160‐fold variation of cyp1a2*1f restriction enzyme CYP450 family, is of interest to many due to its activation of procarcinogens such. 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Women 394 had a daily caffeine intake was estimated as described previously [ 20, 21 ] (..., it is able to metabolize some PAHs to carcinogenic intermediates activity, the!