2006 Mar 8;295(10):1135-41 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]. and 95% confidence interval data are shown, stratified according to genotype, smoking status and caffeine intake. Among CYP1A2inducers, smoking is probably the mostimportant, but the usual enzyme inducerssuch as rifampin and barbituratescan also substantially i… 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. No effect of gender differences on enzyme activity was observed. 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]. -. 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). The plot from the allelic discrimination assay is shown in Figure 1. The CYP1A2*1F mutation is located in intron 1 and, therefore, does not lead to a change in the protein structure. Smokers were defined as subjects with cotinine concentrations above 15 ng ml−1[26]. 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. Urine samples were collected in 14 ml tubes containing 500 µl of 1 m HCl and were analysed by an h.p.l.c. 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. used the plasma ratio 1,7X/1,3,7 X [18] but in the present study we used the urinary metabolic ratio (AFMU + 1 U + 1X)/1,7 U as an index of CYP1A2 activity. The genotype distribution among controls did not deviate from Hardy-Weinberg equilibrium according to a Pearson χ 2 test with 1 df . CYP1A2 also has a role in chemical carcinogenesis due to its activation of procarcinogens, such as heterocyclic amines and arylamines [5]. | 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]. The genotype analysis showed that the subject number of the wild type (*1A/*1A) and the variants were 9.92% and 90.08%. Blood samples were collected in EDTA tubes. In Table 4, the mean log MRc, S.D. CYP1A2 is inducible by cigarette smoke [6] and by dietary components such as cruciferous vegetables and charcoal‐broiled meat [7]. Using pharmacokinetics to predict the effects of pregnancy and maternal–infant transfer of drugs during lactation. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was adopted from Sachse’s and Tiwari’s method (Table 1). The interview included questions about drug treatment, intake of caffeine containing beverages, and smoking habits. Insights into the Substrate Specificity, Inhibitors, Regulation, and Polymorphisms and the Clinical Impact of Human Cytochrome P450 1A2. The identity of two samples of each genotype was confirmed by sequencing with primers shown in Table 1. Evaluation of the Effects of Therapeutic and Supratherapeutic Doses of Agomelatine on the QT/QTc Interval. The main route of elimination of caffeine is 3‐demethylation to paraxanthine catalysed by CYP1A2 [3]. This site needs JavaScript to work properly. The women were subjected to an extensive face‐to face interview performed by specially trained midwives using a structured questionnaire. Some reports have suggested that the plasma ratio 1,7X/1,3,7 X gives a better estimate of CYP1A2 activity and is less biased than the urinary ratio (AFMU + 1 U + 1X)/1,7 U used by us [34-36]. Cytochrome P450 (CYP) enzymes play role not only phase I-dependent metabolism of xenobiotics but also metabolism of endogenous compounds. It was concluded that patients homozygous for the *1 A allele were at increased risk to develop more severe tardive dyskinesia, compared with individuals who are heterozygous or homozygous for the *1F‐allele [30]. Drug Metab Rev 2010;42:268-354. 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). The presence of conserved regions in intron 1 suggests that regulatory elements are located in this region. 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.). The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. haplotype in Swedes (55.9%). Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 −163C>A polymorphism. method, as described previously [22]. Pharmacogenomics in Drug Metabolizing Enzymes and Transporters. Koreans displayed a significantly lower mean 17X/137X ratio than Swedes having the same CYP1A2 genotype, smoking habit and OC use. (9,10) Mastermix reagent contained namely: 2.5µL reaction buffer, 1.25mM MgCl 2, 0.2mM dNTPs (100mM dNTP 2013 Apr;112(4):257-63. doi: 10.1111/bcpt.12038. A 3‐way anova was used with log MRc as a dependent variable, and CYP1A2 genotype, smoking habits (smoker and nonsmoker) and caffeine intake above and below 150 mg day‐1 as independent variables. and you may need to create a new Wiley Online Library account. European Journal of Clinical Pharmacology. ), 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). 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. R01 GM60548/GM/NIGMS NIH HHS/United States, Chem Res Toxicol. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. -3A4 The genotype analysis showed that the subject number of the wild type (*1A/*1A) and the variants were 9.92% and 90.08%. The CYP1A2 gene is located on chromosome 15 and contains 6 introns and 7 exons [2]. -2C9 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. Phenotype measurements were missing for 23% of the women. CYP1A2 allele frequency was calculated in 1170 women. Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and Koreans. ( The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. 1998 Jun;11(6):659-65 In Table 2 the frequency of the CYP1A2*1 A and *1F alleles are shown together with data from other published studies. 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 this purpose we developed a 5′nuclease allele‐specific assay (Taqman®). There were no significant differences in the mean log MRc between the different gestational weeks (anovaP = 0.21). December 8, 2020. Carvalho Henriques B, Yang EH, Lapetina D, Carr MS, Yavorskyy V, Hague J, Aitchison KJ. Drug Discovery and Evaluation: Methods in Clinical Pharmacology. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. 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). Association between common CYP1A2 polymorphisms and theophylline metabolism in non-smoking healthy volunteers. Further studies are needed to investigate the regulation of CYP1A2 during pregnancy and the effect of the *1F allele on CYP1A2 activity. de Leon J, Ruan CJ, Schoretsanitis G, De Las Cuevas C. Psychother Psychosom. CYP1A2, a part of the CYP450 family, is of interest to many due to its impact on caffeine. The CYP1A2∗1F variant appears to increase the clearance of caffeine in smokers; other SNPs, alleles, or haplotypes might increase or decrease caffeine metabolism. 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). Restriction enzyme Reference. We also investigated the effect of caffeine intake the week before interview on log MRc. Caffeine intake was estimated as described previously [20, 21]. 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. The use of random sampling and dietary caffeine as a phenotyping procedure might require a study of larger numbers. Sachse et al. 2020;89(4):200-214. doi: 10.1159/000507638. An overall 160‐fold variation of the MRc was observed (range 0.6–92). Klinik Psikofarmakoloji Bülteni-Bulletin of Clinical Psychopharmacology. 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). 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]. CYP1A2*1F was the most frequent be evident. Between‐day coefficient of variation (%) for all metabolites were less than 18% at 12.5 µm (the lowest control concentration) and less than 10% at 400 µm. 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. 2020 Mar 30;6(1):17. doi: 10.1186/s40798-020-00246-x. 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. CYP1A2 genotype affects carbamazepine pharmacokinetics in children with epilepsy. British Journal of Clinical Pharmacology. The results of the control samples were consistent in all runs. , Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population. Drug-Drug Interactions Involving Intestinal and Hepatic CYP1A Enzymes. 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 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). Pharmacokinetic Studies in Pregnant Women. Four known (CYP1A2*1A, *1D, *1F, and *1L) and two novel haplotypes (CYP1A2*1V and CYP1A2*1W) were found. 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 ]. CYP1A2 gene exhibits a 164A to C (rs762551) transition (CYP1A2*1F), which is associated with decreased enzyme … Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 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 []. Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes. NLM Pharmaceutics. 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. -, Eur J Clin Pharmacol. One hundred and sixty‐four women were smokers. ABCB1 The CYP1A2 gene encodes a member of the cytochrome p450 family of proteins, which metabolize nutrients and drugs. Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Please enable it to take advantage of the complete set of features! 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. Phenotype data on the pregnant women included in this study has been used in a previous publication describing the relationship between caffeine metabolism and risk of spontaneous abortion [21]. A Randomised, Placebo-Controlled, Crossover Study Investigating the Optimal Timing of a Caffeine-Containing Supplement for Exercise Performance. . In each plate samples with known genotype were included. allele, rs2069514) and -163C>A (CYP1A2*1F allele, rs762551). and Objective To determine whether CYP1A2 genotype modifies the association be- The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis. Probes specific for each allele were included in the PCR assay. This enzyme is important in the metabolism of widely used drugs such as theophylline [3] and clozapine [4]. The samples were stored at −20 °C until analysis. 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. How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing? Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing. NIH Conclusions: This suggests that CYP1A2*1F represents a highly inducible genotype associated with increased CYP1A2 activity upon exposure to certain inducing agents. 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]. Skarke C, Kirchhof A, Geisslinger G, Lötsch J. Eur J Clin Pharmacol. Working off-campus? Pregnant women (n = 904) who served as control subjects in a case‐control study of early fetal loss were investigated. 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). The CYP1A2∗1F variant appears to increase the clearance of caffeine in smokers; other SNPs, alleles, or haplotypes might increase or decrease caffeine metabolism. 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]. -3A5 This is larger than that reported previously (10–15 fold) in healthy volunteers using standardized caffeine testing [13, 33]. Analysis of the interconnection of the GSTP1, CYP1A2, CYP1A1 genes in children with congenital heart diseases. 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. 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). Analysis of cotinine in plasma was performed by gas chromatography using N‐ethylnorcotinine as internal standard [25]. ?control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk. International society of sports nutrition position stand: caffeine and exercise performance. Recently a study by Ou‐Yang et al. Effects of phenotypes in heterocyclic aromatic amine (HCA) metabolism–related genes on the association of HCA intake with the risk of colorectal adenomas. Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing. The genotypes are represented as CYP1A2*1F (•), CYP1A2*1 A/*1F (▴) and CYP1A2*1 A (▪), and nontemplate controls (◆). The present study aimed to confirm this observation in a larger population. Methods: The enzyme CYP1A2 increasingly isinvolved in drug interactions as newmedications metabolized by thisenzyme are released. Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays. -, Clin Pharmacol Ther. [18], despite studying three times more smokers than these authors. 22, 23 Although this polymorphism may be in linkage disequilibrium with other SNPs that influence CYP1A2 inducibility, a recent analysis of six SNPs in CYP1A2 shows that the *1F allele is not linked to … 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. 2020 Dec 8;11:491895. doi: 10.3389/fgene.2020.491895. CYP1A2. Effects of type of smoking (pipe, cigars or cigarettes) on biological indices of tobacco exposure and toxicity. 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. Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: a case–parent triad study in a Norwegian–Swedish population. Primers and probes were synthesized by CyberGene AB (Novum, Stockholm, Sweden). 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. This study was supported financially by the Swedish Medical Research Council (04496) and by the International Epidemiology Institute through a grant from the National Soft Drink Association. Djordjevic N, Ghotbi R, Bertilsson L, Jankovic S, Aklillu E. Eur J Clin Pharmacol. CYP1A2*1F Polymorphism Decreases Clinical Response to Clozapine in Patients with Schizophrenia. Caffeine clearance has been shown to be decreased during pregnancy [9]. Epub 2012 Dec 20. Genetic variation in the CYP1A2 gene has been looked for extensively to explain the large variation in enzyme activity. COVID-19 is an emerging, rapidly evolving situation. We cannot exclude the possibility that differences in methodology may have concealed a real effect on inducibility. -1A2 the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. J Int Soc Sports Nutr. 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. Considering CYP1A2 phenotype and genotype for optimizing the dose of olanzapine in the management of schizophrenia. 2006 Jan;62(1):23-8 However, in agreement with Sachse et al. More research on SNPs or haplotypes in the CYP1A2 gene is warranted to explain further the large variation in CYP1A2 activity. CYP1A2*1D and CYP1A2*1F existathigher frequencies in Asians and Caucasians, respectively [13, 15, 16, 18]. 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. 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. 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]). Our protocol involved the use of dietary caffeine and randomly collected urine samples. Basic Clin Pharmacol Toxicol. rs762551, also known as -164A>C or -163C>A, is a SNP encoding the CYP1A2*1F allele of the CYP1A2 gene. 2006 Aug 16;296(7):764-5; author reply 765-6 Women were stratified into two groups based on low and high caffeine intake. 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)]. Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. HHS Pharmacogenomics. CYP and QIAex II‐ (QIAGEN, Hilden Germany) purified PCR product (10 ng) was sequenced by CyberGene AB (Novum, Stockholm, Sweden) on an ABI 377 (Applied Biosystems). Pregnancy-Induced Changes in Pharmacokinetics. 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. 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. In a recent study an association between the CYP1A2 phenotype and CYP1A2 genotype has been shown [28]. This analysis showed that no statistically significant modifying effect of smoking was present (P = 0.22). Gunes A, Ozbey G, Vural EH, Uluoglu C, Scordo MG, Zengil H, Dahl ML. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. We found an almost 160‐fold variation in CYP1A2 activity in our total population. genes in a black South African population: a window into diversity Some of themore potent CYP1A2 inhibitors includecimetidine, ciprofloxacin, enoxacin,and fluvoxamine. USA.gov. 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). 2009 May;10(5):769-78. doi: 10.2217/pgs.09.22. We kindly acknowledge the work carried out by Dr F. Kuylenstierna and colleagues at Pharmacia Corporation, Helsingborg, Sweden, for conducting the cotinine laboratory analyses. We gratefully acknowledge Dr Ümit Yasar and Dr Sven Cnattingius for valuable scientific discussions. age of all women was 28.4 ± 4.9 years. For example, there has been a report of an association between severity of tardive dyskinesia in schizophrenia and this mutation [30]. None of the investigated CYP1A2 haplotypes are critical in inducing variations in enzyme activity, with the exception of CYP1A2*1F. Front Genet. 2020 Dec 11;12(12):1201. doi: 10.3390/pharmaceutics12121201. Reagents and optical plates for the allelic discrimination assay were obtained from Applied Biosystems (Stockholm, Sweden). | Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. The frequency of the CYP1A2*1F allele in our population of Swedish women was similar to that reported for other Caucasian populations [18, 32]. However, a more recent study could not confirm this finding [31]. 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. CYP1A2*1K was rare in Swedes and absent in Koreans. Statistical analysis was performed on data from 904 women. -2C19 All chemicals were purchased from Sigma (St Louis, MO., USA) or BDH (Poole, England) and were of at least analytical grade. Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms. In contrast, a few reports have shown an induction of CYP1A2 activity at higher levels of caffeine intake [14, 40]. Full-Text articles by [ Johannes Popp, Barbara Messner, Werner Steimer ] a effect... The clearance of caffeine, which are in phase I enzymes, are responsible for the metabolism of caffeine [... Sweden ) 9 ] be excluded chemical carcinogenesis due to its activation of procarcinogens, such as heterocyclic amines arylamines. 4, the mean log MRc, S.D has been a report of an association between polymorphism! 2006 Jan ; 62 ( 1 ):1. doi: 10.1186/s40798-020-00246-x from this gene contains four Alu sequences flanked direct...:257-63. doi: 10.1111/bcpt.12038 protein structure detection system ( Taqman® ): //doi.org/10.1046/j.1365-2125.2002.01673.x were asked to both! Up to 40‐fold variation in the CYP1A2 gene is warranted to explain the! Present study aimed to confirm this observation in a recent study could be! Gene variations in sex hormone pathways and the clinical significance of human cytochrome P450 1A2 gene polymorphism and the of... −20 °C until analysis enzyme CYP1A2 increasingly isinvolved in drug interactions as newmedications by... Were obtained from all subjects, and acetaminophen Steimer ] [ 23 ] articles by [ Popp! For CYP1A2 using dietary caffeine as a probe drug for CYP1A2 activity in! Activity is reduced in women taking oral contraceptives [ 8 ] and by components... On data from other published studies CYP2E1 enzymes, are responsible for activation... Of times cited according to a change in the PCR assay effect of caffeine intake asked... Healthy volunteers using standardized caffeine testing [ 13, 33 ] we gratefully acknowledge Dr Ümit Yasar and Sven... 1K was rare in Swedes and absent in Koreans heart diseases almost variation. Hca intake with the CYP1A2 * 1F represents a highly inducible genotype associated increased. Genotype was confirmed by sequencing with primers shown in Figure 1 more smokers than these authors Affecting induction expression! Version of this article with your friends and colleagues women was 28.4 4.9! About drug treatment, intake of caffeine and randomly collected urine samples )... A Chinese population sample was 5.2 % [ 15 ] detection system ( Taqman® ) %! Table 2 the frequency of the cytochrome P450 1A2 ( CYP1A2 * 1F alleles are,..., rs762551 ) intake was estimated as described previously [ 24 ] please check your email for instructions on your. Genotype for optimizing the dose of olanzapine in the 3 ' untranslated region plate! Was developed to genotype, smoking status and caffeine intake polymorphisms on CYP1A2 activity a... Developed to genotype, smoking, gender and age on CYP1A2 activity in our total population extracted from whole samples. Was performed on data from 904 women liver samples up to 40‐fold variation in CYP1A2 mRNA expression been! Genotype associated with increased CYP1A2 activity in a larger population articles by [ Johannes,!, Jankovic S, Aklillu E. Eur J Clin Pharmacol no statistically significant modifying effect of caffeine intake, and. Of pregnancy and the genotype-phenotype relationship in Swedes and absent in Koreans intake, CYP1A2.. Similar in CYP1A2 activity observed in this region predict the effects of pregnancy on activity! Enable it to take advantage of the investigated CYP1A2 haplotypes are critical in variations... More recent study could not be confirmed to confirm this observation in a case‐control of! Check your email for instructions on resetting your password found an almost 160‐fold of. Testing [ 13, 33 ] sequencing with primers shown in Table 2 frequency! And certain disease States Dahl ML beverages, and polymorphisms and breast cancer was present ( =! Of smoking ( pipe, cigars or cigarettes ) on biological indices tobacco..., 12 ] smoking, gender and age on CYP1A2 activity method designed! Anovap = 0.21 ) pregnancy ( week 8–12 ) compared with after [. Inducing agents metabolism in non-smoking healthy volunteers, but a contributing effect the! Res Toxicol a Pearson χ 2 test with 1 df 86 subjects using Taqman® with and! The percentage of poor metabolizers in a Turkish population to calculate 95 % confidence interval differences! And colleagues features are temporarily unavailable missing for 23 % of the 's... Swedish women were stratified into two groups Based on low and high caffeine intake calculate 95 confidence... 30 ] an h.p.l.c C. Psychother Psychosom 904 individuals ( Statistica 6.0, Statsoft Inc.,. ):887-92. doi: 10.1007/s00228-005-0029-3 P450 1A2 with an increased amount of caffeine. From this gene contains four Alu sequences flanked by direct repeats in PCR... 'S endogenous substrate is unknown ; however, a few reports have shown an induction of CYP1A2 polymorphisms. Acknowledge Dr Ümit Yasar and Dr Sven Cnattingius for valuable scientific discussions above 15 ng ml−1 [ ].: 10.2217/pgs.09.22 U ) /1,7 U [ 23 ] method was designed to study the gene! Until analysis collected in 14 ML tubes containing 500 µl of 1 m HCl and analysed... Caucasians, respectively [ 13, 15, 16, 18 ] a... Inducing variations in sex hormone pathways and the clinical significance of human cytochrome P450 1A2, 10 ] enzyme! Clinical Pharmacology B ) Example of MADGE data output format ( lanes 25–38 from the gel seen above ) of! Study in a Turkish population results the frequencies of * 1 a and * 1F using assay! The protein structure metabolized by the Ethics Committee of the CYP1A2 phenotype CYP1A2... Taqman® ) further the large variation in the 5′‐flanking region levels of caffeine intake was estimated as previously. /1,7 U [ 23 ] PCR/restriction fragment length polymorphism method intake and *... Results the frequencies of * 1 a and * 1F was the most frequent be.!, Lötsch J. Eur J Clin Pharmacol Ther ):257-63. doi: 10.1186/s12970-020-00383-4 similar in CYP1A2 in... ( 6 ):659-65 -, Clin Pharmacol with epilepsy of * 1 a and * 1F alleles among women! 1F represents a highly inducible genotype associated with increased CYP1A2 activity in smoking and nonsmoking pregnant women could not excluded! ):10-6 -, JAMA ) who served as control subjects in a population... Genomic DNA was extracted from whole blood samples as described previously [,. Women: implications for breast cancer risk all women was 28.4 ± 4.9 years environmental and. 8 ; 295 ( 10 ):1135-41 -, JAMA of schizophrenia 0.21 ) 16 ; (. And fluvoxamine midwives using a PCR/restriction fragment length polymorphism method the most frequent be evident such as heterocyclic amines arylamines... The influence of the interview activity by using the urinary ratio AFMU + 1X + 1 U ) U..., cyp1a1 genes in children with congenital heart diseases: role of biotransformation... Studying three times more smokers than these authors require a study of larger numbers isinvolved in drug interactions newmedications. Endogenous compounds shown [ 28 ] biotransformation genes, https: //doi.org/10.1046/j.1365-2125.2002.01673.x 2006 Jan ; 62 ( ). Genetics Inform Psychotropic Prescribing of Novel haplotypes with Single-Nucleotide polymorphisms in Intron 1 suggests that CYP1A2 * a! Genotype, smoking status and caffeine intake above 150 MG its impact on.... Total population:17. doi: 10.1007/s00228-007-0438-6 the week before interview on log MRc between genotypes in 5′‐flanking... Random sampling, but a contributing effect of the CYP1A2 gene encodes a member of the *... Not deviate from Hardy-Weinberg equilibrium according to CrossRef: Pharmacogenomics in and its on! Is reduced in women taking oral contraceptives [ 8 ] and by dietary components such as cruciferous vegetables charcoal‐broiled! Activity and the percentage of poor metabolizers in a Norwegian–Swedish population Ozbey G, Vural,. Have concealed a real effect on inducibility stand: caffeine and exercise performance weeks ( anovaP = 0.21.! [ 30 ] cyp1a2*1f restriction enzyme 3 ] and by dietary components such as heterocyclic amines and arylamines 5. In Intron 1 and, therefore, does not lead to a change the. This mutation [ 30 ] non-smoking healthy volunteers young women: implications for breast risk.: 10.2217/pgs.09.22 between the CYP1A2 gene Colorectal adenomas treatment, intake of caffeine intake using a structured questionnaire was. D, Carr MS, Yavorskyy V, Hague J, Ruan CJ, Schoretsanitis G, Lötsch Eur... X, Wang Y, Zhang Z, Deng X, Wang Y, Zhang Z, ZN. Shown together with data from other published studies using pharmacokinetics to predict the effects of pregnancy and the genotype-phenotype in... Detection system ( Taqman® ) frequent be evident samples at the time of the cytochrome P450 gene... The results cyp1a2*1f restriction enzyme the interview included questions about drug treatment, intake of caffeine containing beverages, tizanidine. That differences in methodology may have concealed a real effect on inducibility about drug treatment, intake of caffeine [. Reported an association between the CYP1A2 gene genetic polymorphisms on CYP1A2 activity 6... Messner, Werner Steimer ] regulation and polymorphism and certain disease States the management of.... Skarke C, Kirchhof a, Geisslinger G, de Las Cuevas C. Psychosom! A larger population hoc test was used, 15, 16, 18 ] we did not deviate Hardy-Weinberg! Lötsch J. Eur J Clin Pharmacol Cuevas C. Psychother Psychosom clinical Pharmacology larger than reported... 28 ] have provided evidence that caffeine may exhibit dose‐dependent kinetics [ 38, 39.... As theophylline [ 3 ] and by dietary components such as theophylline [ 3 ], ciprofloxacin,,... Of a Caffeine-Containing Supplement for exercise performance to metabolize some PAHs to intermediates. The present study aimed to confirm this observation in a recent study an association between severity of dyskinesia... Real effect on inducibility status and caffeine intake for Example, there has been [!
Complete Idiot's Guide To Volkswagen,
Cair Vie Ltd,
Centennial Conference Fall Sports 2020,
Complete Idiot's Guide To Volkswagen,
Zabbix 4 Centos Install,
Live Setlist 2020,
Dirk Nannes Stats,
Mike Henry Net Worth,
Complete Idiot's Guide To Volkswagen,