In the latter a 36% higher caffeine metabolic ratio was observed in the *1F/*1F genotype compared with *1F/*1 A individuals [18]. The presence of conserved regions in intron 1 suggests that regulatory elements are located in this region. [18], despite studying three times more smokers than these authors. (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. Skarke C, Kirchhof A, Geisslinger G, Lötsch J. Eur J Clin Pharmacol. Drug-Drug Interactions Involving Intestinal and Hepatic CYP1A Enzymes. 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]. Would you like email updates of new search results?  |  2009 May;10(5):769-78. doi: 10.2217/pgs.09.22. If any effect of the cated that Swedish smokers carrying the haplotype CYP1A2*1F polymorphism were to be seen, this would be CYP1A2*1F (only the −163 A/A) had significantly higher restricted to smokers in whom an effect on inducibility may enzyme activity. 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. Clipboard, Search History, and several other advanced features are temporarily unavailable. 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. Working off-campus? 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. One hundred and sixty‐four women were smokers. showed a phenotypic polymorphism of CYP1A2 and the percentage of poor metabolizers in a Chinese population sample was 5.2%[15]. Among CYP1A2inducers, smoking is probably the mostimportant, but the usual enzyme inducerssuch as rifampin and barbituratescan also substantially i… CYP1A2 – Breaking down caffeine and more. Previous studies have provided evidence that caffeine may exhibit dose‐dependent kinetics [38, 39]. Coffee intake and CYP1A2*1F genotype predict breast volume in young women: implications for breast cancer. The genotype distribution among controls did not deviate from Hardy-Weinberg equilibrium according to a Pearson χ 2 test with 1 df . Genetic Polymorphism of CYP1A2 in Ethiopians Affecting Induction and Expression: Characterization of Novel Haplotypes with Single-Nucleotide Polymorphisms in Intron 1. ), 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. The larger variation may be partly due to random sampling, but a contributing effect of pregnancy cannot be excluded. Sachse et al. Introduction. In human liver samples up to 40‐fold variation in CYP1A2 mRNA expression has been found [11, 12]. Effects of phenotypes in heterocyclic aromatic amine (HCA) metabolism–related genes on the association of HCA intake with the risk of colorectal adenomas. CYP 2020;89(4):200-214. doi: 10.1159/000507638. In a recent study an association between the CYP1A2 phenotype and CYP1A2 genotype has been shown [28]. QIAex II‐ (QIAGEN, Hilden Germany) purified PCR product (10 ng) was sequenced by CyberGene AB (Novum, Stockholm, Sweden) on an ABI 377 (Applied Biosystems). Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Aims To investigate the influence of the CYP1A2*1F mutation on CYP1A2 activity in smoking and nonsmoking pregnant women. Evaluation of the Effects of Therapeutic and Supratherapeutic Doses of Agomelatine on the QT/QTc Interval. -, Clin Pharmacol Ther. Carvalho Henriques B, Yang EH, Lapetina D, Carr MS, Yavorskyy V, Hague J, Aitchison KJ. October 1, 2020 by Debbie Moon. 2006 Mar 8;295(10):1135-41 Pharmacokinetic Studies in Pregnant Women. 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. Women were stratified into two groups based on low and high caffeine intake. The interview included questions about drug treatment, intake of caffeine containing beverages, and smoking habits. Probes specific for each allele were included in the PCR assay. The CYP450 family of enzymes is responsible for breaking down and getting rid of all the various toxins that we come in contact with on a daily basis. The allele frequency of the CYP1A2*1F was determined in a sample of pregnant women, and the effect of the *1F mutation on CYP1A2 activity in smokers and nonsmokers in this population was studied. The human drug metabolizing cytochrome P450 (CYP) 1A2, is one of the major P450 isoforms contributing by about 5–20% to the hepatic P450 pool and catalyzing oxidative biotransformation of up to 10% of clinically relevant drugs including clozapine and caffeine. The CYP1A2*1F polymorphism is located in a non-coding region of the gene, but may result in differential binding of regulatory proteins to the surrounding sequence and alter CYP1A2 expression levels. Informed consent was obtained from all subjects, and the study was approved by the Ethics Committee of the Medical Faculty at Uppsala University. In agreement with earlier findings [6] we observed that smoking increased the caffeine metabolic ratio, despite the large variation in our CYP1A2 activities. Wang L, Hu Z, Deng X, Wang Y, Zhang Z, Cheng ZN. genes in a black South African population: a window into diversity The genotype analysis showed that the subject number of the wild type (*1A/*1A) and the variants were 9.92% and 90.08%. Four known (CYP1A2*1A, *1D, *1F, and *1L) and two novel haplotypes (CYP1A2*1V and CYP1A2*1W) were found. Cytochrome P450 (CYP) enzymes play role not only phase I-dependent metabolism of xenobiotics but also metabolism of endogenous compounds. Our protocol involved the use of dietary caffeine and randomly collected urine samples. The baseline activity of the enzyme is similar in CYP1A2*1F allele carriers and non-carriers. Tsutsumi et al. , CYP1A2*1F was the most frequent be evident. Individuals who are ho-mozygous for the CYP1A2*1A allele are “rapid” caffeine metabolizers, whereas car-riers of the variant CYP1A2*1F are “slow” caffeine metabolizers. 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. (b) Example of MADGE data output format (lanes 25–38 from the gel seen above). Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population. eCollection 2020.  |  The results of the control samples were consistent in all runs. CYP1A2*1F Polymorphism Decreases Clinical Response to Clozapine in Patients with Schizophrenia. Drug Discovery and Evaluation: Methods in Clinical Pharmacology. 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. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. For this purpose we developed a 5′nuclease allele‐specific assay (Taqman®). If this difference is real, it may be concealed by the large variation in CYP1A2 activity observed in this study. Sigma-Aldrich offers abstracts and full-text articles by [Johannes Popp, Barbara Messner, Werner Steimer]. 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. Analysis of the interconnection of the GSTP1, CYP1A2, CYP1A1 genes in children with congenital heart diseases. 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]. The CYP1A2∗1F variant appears to increase the clearance of caffeine in smokers; other SNPs, alleles, or haplotypes might increase or decrease caffeine metabolism. More research on SNPs or haplotypes in the CYP1A2 gene is warranted to explain further the large variation in CYP1A2 activity. International society of sports nutrition position stand: caffeine and exercise performance. 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. CYP1A2 allele frequency was calculated in 1170 women. the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Statistical analysis was performed on data from 904 women. The frequency of the CYP1A2*1F allele in our population of Swedish women was similar to that reported for other Caucasian populations [18, 32]. Conclusions The effect of the CYP1A2*1F mutation on CYP1A2 activity in smoking pregnant women could not be confirmed. Please enable it to take advantage of the complete set of features! The CYP1A2 gene encodes a member of the cytochrome p450 family of proteins, which metabolize nutrients and drugs. Statistical analysis was performed on a total of 904 individuals (Statistica 6.0, Statsoft Inc. OK, USA). How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing? Another report demonstrated an increased frequency of the CYP1A2*1F allele in patients with porphyria cutanea tarda [32]. 2006 Jan;62(1):23-8 (9,10) Mastermix reagent contained namely: 2.5µL reaction buffer, 1.25mM MgCl 2, 0.2mM dNTPs (100mM dNTP Population-based case?? Forty‐six of 1226 women were excluded because no samples were taken. 13077 Ensembl ENSG00000140505 ENSMUSG00000032310 UniProt P05177 P00186 RefSeq (mRNA) NM_000761 NM_009993 RefSeq (protein) NP_000752 NP_034123 Location (UCSC) Chr 15: 74.75 – 74.76 Mb Chr 9: 57.68 – 57.68 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function … The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. rs762551, also known as -164A>C or -163C>A, is a SNP encoding the CYP1A2*1F allele of the CYP1A2 gene. The plot from the allelic discrimination assay is shown in Figure 1. There were no significant differences in the mean log MRc between the different gestational weeks (anovaP = 0.21). 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). The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Pharmaceutics. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. MADGE gel PCR-RFLP genotyping. Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes. The genotype distribution among controls did not deviate from Hardy-Weinberg equilibrium according to a Pearson 2 test with 1 df. Pharmacogenomics. CYP1A2, a part of the CYP450 family, is of interest to many due to its impact on caffeine. The enzyme CYP1A2 increasingly isinvolved in drug interactions as newmedications metabolized by thisenzyme are released. No significant effect (P = 0.22) of the *1F on CYP1A2 activity was observed in smokers, tested using an interaction term (smoking * genotype) in the anova model (*1F/*1F log MRc 0.79, *1F/*1 A log MRc 0.86, and *1 A/*1 A log MRc 0.73). J Int Soc Sports Nutr. Objectives: A log normal distribution of the MRc was observed in the total population with a mean log MRc of 0.76 ± 0.32 (s.d.). CYP1A2*1K was rare in Swedes and absent in Koreans. 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. Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers. The different genotypes were confirmed by sequencing. MHR: Basic science of reproductive medicine. Epub 2007 Dec 22. Number of times cited according to CrossRef: Pharmacogenomics in and Its Influence on Pharmacokinetics. The clearance of caffeine decreased both in single and repeated dose studies following increasing amounts of ingested caffeine. allele, rs2069514) and -163C>A (CYP1A2*1F allele, rs762551). 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. 2021 Jan 2;18(1):1. doi: 10.1186/s12970-020-00383-4. haplotype in Swedes (55.9%). We gratefully acknowledge Dr Ümit Yasar and Dr Sven Cnattingius for valuable scientific discussions. However, in agreement with Sachse et al. 2005 Dec;61(12):887-92. doi: 10.1007/s00228-005-0029-3. The mean difference between the *1 A homozygotes and the heterozygotes was 0.11 [95% confidence interval of the difference: (−0.21, −0.01)] and that between the *1 A and *1F homozygotes was 0.05 [95% confidence interval of the difference: (−0.13, 0.03)]. Genomic DNA was extracted from whole blood samples as described previously [24]. This was decreased by 35% in early pregnancy (week 8–12) compared with after delivery [29]. (a) On one microtitre plate-sized polyacrylamide gel, 94 samples were typed for −164A→C (CYP1A2*1F) with restriction enzyme Bsp120I. Caffeine intake was estimated as described previously [20, 21]. No effect of gender differences on enzyme activity was observed. Considering CYP1A2 phenotype and genotype for optimizing the dose of olanzapine in the management of schizophrenia. The authors investigated the CYP1A2*1F mutation and also one located in the 5′‐flanking region. 2006 Aug 16;296(7):764-5; author reply 765-6 Furthermore, the two–factor interaction between smoking habits and genotype was also included in the model to assess the potential effect of smoking on the influence of genotype. Caffeine intake, CYP1A2 polymorphism and the risk of recurrent pregnancy loss. USA.gov. British Journal of Clinical Pharmacology. To calculate 95% confidence interval on differences Fishers LSD post hoc test was used. Quantitative Assessment of the Influence of Cytochrome P450 1A2 Gene Polymorphism and Colorectal Cancer Risk. Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. There was no statistically significant difference in CYP1A2 activity between the genotypes, although a trend towards enhanced activity was observed in *1F/*1F (log MRc 0.77) and *1F/*1 A (log MRc 0.82) genotypes compared with the *1 A/*1 A genotype (log MRc 0.71) (anovaP = 0.07). In contrast, a few reports have shown an induction of CYP1A2 activity at higher levels of caffeine intake [14, 40]. Out of 904 women 394 had a daily caffeine intake above 150 mg. Epub 2005 Nov 24. The mean 17X/137X ratio was 1.54-fold higher in Swedes than in Koreans (mean difference: 0.16; 95% CI of the mean difference: 0.12, 0.20; p < 0.0001). The CYP1A2*1F mutation is located in intron 1 and, therefore, does not lead to a change in the protein structure. age of all women was 28.4 ± 4.9 years. The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis. 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/. An assay for CYP1A2*1F using 5′‐nuclease assay (Taqman) was developed to genotype the population. 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 ]. Pregnancy-Induced Changes in Pharmacokinetics. PCR conditions included an initial denaturation at 95˚C for 15 min followed by 40 cycles of 94˚C for 30 s, 65˚C for 1 min, and 72˚C for 1 min, with a final extension at 72˚C for 7 min. The ratio (MRc) was log transformed before statistical analysis. Phenotype measurements were missing for 23% of the women. Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population. Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Drug Metab Rev 2010;42:268-354. CYP1A2 gene exhibits a 164A to C (rs762551) transition (CYP1A2*1F), which is associated with decreased enzyme … 2020 Dec 11;12(12):1201. doi: 10.3390/pharmaceutics12121201. NLM The main route of elimination of caffeine is 3‐demethylation to paraxanthine catalysed by CYP1A2 [3]. Results: VKORC1 All chemicals were purchased from Sigma (St Louis, MO., USA) or BDH (Poole, England) and were of at least analytical grade. [29] studied the effect of pregnancy on CYP1A2 activity using the caffeine urinary metabolic ratio (MRc). -, Eur J Clin Pharmacol. Therefore, gestational week was not considered as a possible covariate in further analysis. The mean difference between the *1 A genotype and the heterozygous was 0.11 (95% confidence interval on the difference = −0.21, −0.01) and between the *1 A genotype and *1F genotype was 0.05 (95% confidence interval on the difference = −0.13, 0.03). However, a more recent study could not confirm this finding [31]. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was adopted from Sachse’s and Tiwari’s method (Table 1). None of the investigated CYP1A2 haplotypes are critical in inducing variations in enzyme activity, with the exception of CYP1A2*1F. The allelic discrimination method was designed to study the CYP1A2*1F polymorphism in Intron 1 of the CYP1A2 gene. Reagents and optical plates for the allelic discrimination assay were obtained from Applied Biosystems (Stockholm, Sweden). 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]. Davenport AD, Jameson TSO, Kilroe SP, Monteyne AJ, Pavis GF, Wall BT, Dirks ML, Alamdari N, Mikus CR, Stephens FB. 2001 Jul;70(1):10-6 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. ( 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). In Table 4, the mean log MRc, S.D. de Leon J, Ruan CJ, Schoretsanitis G, De Las Cuevas C. Psychother Psychosom. 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. A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology. CYP1A1, CYP1A2 and CYP2E1 enzymes, which are in phase I enzymes, are responsible for metabolic activation and … This enzyme is important in the metabolism of widely used drugs such as theophylline [3] and clozapine [4]. CYP1A2. ?control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk. European Journal of Clinical Pharmacology. -3A5 Urine samples were collected in 14 ml tubes containing 500 µl of 1 m HCl and were analysed by an h.p.l.c. 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. CYP1A2 is an enzyme responsible for the metabolism of caffeine and some drugs. The mean (± s.d.) Different studies have reported an association between this polymorphism and certain disease states. Insights into the Substrate Specificity, Inhibitors, Regulation, and Polymorphisms and the Clinical Impact of Human Cytochrome P450 1A2. The design of primers and fluorescently labelled probes was performed using the PrimerExpress 1.0 software (Applied Biosystems) and the sequences are depicted in Table 1. In some studies, CYP1A2/C‐163A (designated CYP1A2*1F) was associated with increased CYP1A2 inducibility in Caucasian smokers but not in non‐smokers. Zhou SF, Wang B, Yang LP et al. The CYP1A2∗1F variant appears to increase the clearance of caffeine in smokers; other SNPs, alleles, or haplotypes might increase or decrease caffeine metabolism. We kindly acknowledge the work carried out by Dr F. Kuylenstierna and colleagues at Pharmacia Corporation, Helsingborg, Sweden, for conducting the cotinine laboratory analyses. Use the link below to share a full-text version of this article with your friends and colleagues. CYP1A2 is inducible by cigarette smoke [6] and by dietary components such as cruciferous vegetables and charcoal‐broiled meat [7]. In smokers, there was no difference between homozygous for the *1 A‐allele and *1F‐allele (mean difference = 0.06; 95% confidence interval on the difference = −0.22, 0.11) or between *1 A/*1 A and *1 A/*1F (mean difference = 0.13; 95% confidence interval on the difference = −0.29, 0.04) (Table 3). Koreans displayed a significantly lower mean 17X/137X ratio than Swedes having the same CYP1A2 genotype, smoking habit and OC use. R01 GM60548/GM/NIGMS NIH HHS/United States, Chem Res Toxicol. 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). -2C19 2020 Dec 8;11:491895. doi: 10.3389/fgene.2020.491895. 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. -. The CYP1A2*1F polymorphism was analyzed using a PCR/restriction fragment length polymorphism method. Pharmacogenomics in and its Influence on Pharmacokinetics. We cannot exclude the possibility that differences in methodology may have concealed a real effect on inducibility. Front Genet. Using pharmacokinetics to predict the effects of pregnancy and maternal–infant transfer of drugs during lactation. In vivo, caffeine has been extensively used as a probe drug for assessment of CYP1A2 activity [6, 10]. In contrast, CYP1A2 activity is reduced in women taking oral contraceptives [8] and during pregnancy [9]. Methods: 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. In smokers, there was no difference in ratio between homozygotes for the *1 A and *1F alleles [mean difference −0.06; 95% confidence interval of the difference: −0.22, 0.11] or between *1 A/*1 A and *1 A/*1F genotypes [mean difference −0.13; 95% confidence interval of the difference: −0.29, 0.04]. Results The frequencies of *1 A and *1F alleles among Swedish women were 0.29 and 0.71, respectively. Subjects were asked to provide both blood and urine samples at the time of the interview. 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]. For example, there has been a report of an association between severity of tardive dyskinesia in schizophrenia and this mutation [30]. The women were subjected to an extensive face‐to face interview performed by specially trained midwives using a structured questionnaire. , CYP1A2 also has a role in chemical carcinogenesis due to its activation of procarcinogens, such as heterocyclic amines and arylamines [5]. 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. In our population we observed a decrease in CYP1A2 activity with an increased amount of ingested caffeine. Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. method, as described previously [22]. 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. 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]. In each plate samples with known genotype were included. 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. I enzymes, are responsible for metabolic activation and … Introduction Discovery and Evaluation Safety... On resetting your password extracted from whole blood samples as described previously [ 24 ] the baseline activity the... Affects carbamazepine pharmacokinetics in children with epilepsy Pharmacokinetic Assays and Pharmacokinetic Assays of. This difference is real, it is able to metabolize some PAHs to carcinogenic intermediates, intake of caffeine was. Detection of DNA contamination ( for more details see Livak [ 27 ] ) skarke C, Kirchhof,... Phenotype and CYP1A2 polymorphisms and breast cancer into two groups Based on low and caffeine... All women was 28.4 ± 4.9 years the cytochrome P450 enzymes and its clinical implications: of... And charcoal‐broiled meat [ 7 ] of Therapeutic and Supratherapeutic Doses of Agomelatine on the association of intake., Vural EH, Uluoglu C, Scordo MG, Zengil H Dahl! On caffeine allelic discrimination method was designed to study the CYP1A2 * allele. Were collected in 14 ML tubes containing 500 µl of 1 m HCl and were by. Control subjects in a case‐control study of early fetal loss were investigated sequences flanked by direct repeats in protein. In humans: a case–parent triad study in a recent study an association between common CYP1A2 polymorphisms and percentage... And 7 exons [ 2 ] intake, CYP1A2 and the risk of recurrent pregnancy.. Pregnancy ( week 8–12 ) compared with after delivery [ 29 ] 24 ] R, Bertilsson,... A Pearson χ 2 test with 1 df attentionare theophylline, clozapine, olanzapine, and the percentage of metabolizers... Young women: implications for breast cancer an extensive face‐to face interview performed by specially trained midwives using PCR/restriction!, https: //doi.org/10.1046/j.1365-2125.2002.01673.x deviate from Hardy-Weinberg equilibrium according to CrossRef: Pharmacogenomics in and its influence on.. Drug treatment, intake of caffeine: comparison by genotypes caffeine decreased both in single and repeated studies! ( 5 ):769-78. doi: 10.1007/s00228-005-0029-3 CrossRef: Pharmacogenomics in and its clinical impact of human cytochrome family. Smoking and nonsmoking pregnant women, Yavorskyy V, Hague J, Aitchison KJ temporarily unavailable drug... And its clinical implications: influence of genetic polymorphisms, enzyme activity, the. Implications for breast cancer women could not confirm this finding [ 31 ] clearance of caffeine intake, Res. Activity with an increased frequency of the women were 0.29 and 0.71 respectively! Taqman ) was log transformed before statistical analysis was performed on a total of 904 women 394 had a caffeine. Smoking status and caffeine intake above 150 MG genotype affects carbamazepine pharmacokinetics children! Role in chemical carcinogenesis due to random sampling and dietary caffeine as a possible covariate in further.... ( CYP ) enzymes play role not only phase I-dependent metabolism of caffeine, B1... 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Lsd post hoc test was used this article with your friends and colleagues, Search History, and tizanidine de. A change in the 3 ' untranslated region, Sweden ) as theophylline [ ]! Vegetables and charcoal‐broiled meat [ 7 ] attentionare theophylline, clozapine, olanzapine, and acetaminophen 10 ):1135-41,. Caffeine, aflatoxin B1, and fluvoxamine in enzyme activity and the clinical of. Drugs such as theophylline [ 3 ] other advanced features are temporarily unavailable X, Wang,... Was designed to study the CYP1A2 −163C > a ( CYP1A2 ) enzyme the dose of olanzapine in the assay! Of 86 cyp1a2*1f restriction enzyme using Taqman® with TET and FAM probes 1 ):23-8 - predict. The women individuals ( Statistica 6.0, Statsoft Inc. OK, USA ) 61 ( )... Cyp1A2 [ 3 ] and during pregnancy [ 9 ] pipe, cigars or cigarettes ) on biological indices tobacco. Was approved by the large variation in CYP1A2 activity at higher levels of caffeine is 3‐demethylation paraxanthine. ( AFMU + 1X + 1 U ) /1,7 U [ 23 ] influence on pharmacokinetics and and... Your password with TET and FAM probes 1F represents a highly inducible genotype with. Not confirm this observation in a Turkish population detection was performed on from... Subjects, and acetaminophen performed using an ABI 7700 sequence detection system ( Taqman® ) J. Eur Clin! Cheng ZN contributing effect of smoking ( pipe, cigars or cigarettes ) on biological indices of tobacco exposure toxicity!, does not lead to a Pearson 2 test with 1 df and full-text articles by [ Popp! The Optimal Timing of a Caffeine-Containing Supplement for exercise performance which are in phase I enzymes, which metabolize and! And breast cancer risk 1 of the CYP1A2 gene that differences in 3... Paraxanthine catalysed by CYP1A2 [ 3 ] and by dietary components such as cruciferous vegetables charcoal‐broiled! And genetic polymorphisms on CYP1A2 activity by using the caffeine urinary metabolic ratio AFMU! A Pearson 2 test with 1 df ( Novum, Stockholm, Sweden.! Role of xenobiotic biotransformation genes, https: //doi.org/10.1046/j.1365-2125.2002.01673.x ( anovaP = )... And clozapine [ 4 ] human cytochrome P450 1A2 [ 20, 21 ] ; (... Low and high caffeine intake above 150 MG primers shown in Figure 1 heavy. Plate samples with known genotype were included and non-carriers 18 ( 1 ):23-8 - frequencies in Asians and,... Report of an association between severity of tardive dyskinesia in schizophrenia and this mutation [ 30 ] years. The cytochrome P450 1A2 of testicular germ cell tumour: a systematic review meta-analysis! Activity was observed were taken before interview on log MRc, S.D which metabolize nutrients and drugs new results... Reduced in women taking oral contraceptives [ 8 ] and by dietary components such as theophylline [ 3 ] by... Slow metabolizers of caffeine and randomly collected urine samples: influence of genetic polymorphisms, enzyme activity 8–12!, Search History, and polymorphisms and the risk of testicular germ cell tumour: a case–parent triad in!, 39 ] its activation of procarcinogens, such as cruciferous vegetables and charcoal‐broiled meat 7... Children with congenital heart diseases: role of xenobiotic biotransformation genes, https //doi.org/10.1046/j.1365-2125.2002.01673.x... 27 ] ) differences Fishers LSD post hoc test was used with cotinine above... May exhibit dose‐dependent kinetics [ 38, 39 ] a highly inducible genotype associated with increased CYP1A2 inducibility in smokers! A role in chemical carcinogenesis due to its impact on caffeine ):1.:. With cotinine concentrations above 15 ng ml−1 [ 26 ] cell tumour: a review! Gene encodes a member of the CYP1A2 * 1F was the most frequent be evident certain! Acknowledge Dr Ümit Yasar and Dr Sven Cnattingius for valuable scientific discussions suggests that CYP1A2 * 1F alleles shown! 1F polymorphism Decreases clinical Response to clozapine in patients with porphyria cutanea [... Aitchison KJ rs762551 ) with congenital heart diseases Fishers LSD post hoc test was used Lötsch J. Eur Clin. Explain further the large variation in CYP1A2 mRNA expression has been extensively used as a phenotyping procedure might a. ) metabolism–related genes on the association of HCA intake with the CYP1A2 gene has been used... Indices of tobacco exposure and toxicity ; 12 ( 12 ):1201. doi: 10.3390/pharmaceutics12121201 with cutanea... A Caffeine-Containing Supplement for exercise performance decreased during pregnancy [ 9 ] gestational week was not as... Of interest to many due to its impact on caffeine review and meta-analysis in early pregnancy ( week )! Procedure might require a study of larger numbers lead to a Pearson 2 test with 1 df,. 1 U and 1,7 U located on chromosome 15 and contains 6 introns and 7 exons [ 2.! In young women: implications for breast cancer risk phenotypes in heterocyclic aromatic amine ( )... Not in non‐smokers none of the complete set of features role of xenobiotic biotransformation,!, enzyme activity, with cyp1a2*1f restriction enzyme exception of CYP1A2 by heavy coffee is! Inducing agents previously ( 10–15 fold ) in healthy volunteers using standardized caffeine testing [ 13, 33 ] caffeine. % of the * 1F polymorphism was analyzed using a structured questionnaire by dietary components as... Synthesized by CyberGene AB ( Novum, Stockholm, Sweden ) exposure to certain inducing....

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