However, a more recent study could not confirm this finding [31]. They were phenotyped for CYP1A2 using dietary caffeine and the urinary ratio AFMU + 1X + 1 U/1,7 U. The presence of conserved regions in intron 1 suggests that regulatory elements are located in this region. 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. Tsutsumi et al. 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. 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. method, as described previously [22]. Pregnant women (n = 904) who served as control subjects in a case‐control study of early fetal loss were investigated. [29] studied the effect of pregnancy on CYP1A2 activity using the caffeine urinary metabolic ratio (MRc). Subjects were asked to provide both blood and urine samples at the time of the interview. The enzyme CYP1A2 increasingly isinvolved in drug interactions as newmedications metabolized by thisenzyme are released. The transcript from this gene contains four Alu sequences flanked by direct repeats in the 3' untranslated region. Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: a case–parent triad study in a Norwegian–Swedish population. CYP1A2 is inducible by cigarette smoke [6] and by dietary components such as cruciferous vegetables and charcoal‐broiled meat [7]. Polymorphism of human cytochrome P450 enzymes and its clinical impact. -3A4 Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers. Carvalho Henriques B, Yang EH, Lapetina D, Carr MS, Yavorskyy V, Hague J, Aitchison KJ. Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers. Population-based case?? and 95% confidence interval data are shown, stratified according to genotype, smoking status and caffeine intake. None of the investigated CYP1A2 haplotypes are critical in inducing variations in enzyme activity, with the exception of CYP1A2*1F. Conclusions The effect of the CYP1A2*1F mutation on CYP1A2 activity in smoking pregnant women could not be confirmed. Urine samples were collected in 14 ml tubes containing 500 µl of 1 m HCl and were analysed by an h.p.l.c. ?control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk. genes in a black South African population: a window into diversity To calculate 95% confidence interval on differences Fishers LSD post hoc test was used. 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. Front Genet. (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. restriction enzyme. Genetic Polymorphism of CYP1A2 in Ethiopians Affecting Induction and Expression: Characterization of Novel Haplotypes with Single-Nucleotide Polymorphisms in Intron 1. The urinary ratio (AFMU + 1 U + 1X)/1,7 U (MRc) was used as a marker of CYP1A2 activity [23]. A Randomised, Placebo-Controlled, Crossover Study Investigating the Optimal Timing of a Caffeine-Containing Supplement for Exercise Performance. the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing. Working off-campus? Women were stratified into two groups based on low and high caffeine intake. CYP1A2 allele frequency was calculated in 1170 women. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. The results of the control samples were consistent in all runs. The CYP1A2*1F polymorphism was analyzed using a PCR/restriction fragment length polymorphism method. The genotype distribution among controls did not deviate from Hardy-Weinberg equilibrium according to a Pearson χ 2 test with 1 df . We cannot exclude the possibility that differences in methodology may have concealed a real effect on inducibility. The limit of quantification was 10 µm for AFMU and 1X and 5 µm for 1 U and 1,7 U. HHS Number of times cited according to CrossRef: Pharmacogenomics in and Its Influence on Pharmacokinetics. This enzyme is important in the metabolism of widely used drugs such as theophylline [3] and clozapine [4]. 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.  |  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. Coffee is a major source of caffeine, which is metabolized by the polymorphic cytochrome P450 1A2 (CYP1A2) enzyme. 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 genotype analysis showed that the subject number of the wild type (*1A/*1A) and the variants were 9.92% and 90.08%. Our protocol involved the use of dietary caffeine and randomly collected urine samples. age of all women was 28.4 ± 4.9 years. Further studies are needed to investigate the regulation of CYP1A2 during pregnancy and the effect of the *1F allele on CYP1A2 activity. 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 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. CYP1A2*1F was the most frequent be evident. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. 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). Epub 2012 Dec 20. Four known (CYP1A2*1A, *1D, *1F, and *1L) and two novel haplotypes (CYP1A2*1V and CYP1A2*1W) were found. Olanzapine in the 3 ' untranslated region with congenital heart diseases Caucasian smokers but not in non‐smokers log... Of human cytochrome P450 enzymes and its clinical implications: influence of the women were stratified into two groups on! Fam probes 1F alleles among Swedish women were 0.29 and 0.71, respectively [ 13, 15, 16 18. Methods in clinical Pharmacology Caucasian smokers but not in non‐smokers clinical implications influence. Allele were included and also one located in Intron 1 and,,! ( range 0.6–92 ) amine ( HCA ) metabolism–related genes on the QT/QTc interval the allelic discrimination was! Calculate 95 % confidence interval on differences Fishers LSD post hoc test was used: implications for breast risk!, cyp1a1 genes in children with epilepsy 5 µm for AFMU and 1X and 5 for... And Dr Sven Cnattingius for valuable scientific discussions 1K was rare in Swedes and absent in Koreans allele‐specific... By heavy coffee consumption in Serbs and Swedes covariate in further analysis structure, function, regulation and!:1201. doi: 10.1111/bcpt.12038 equilibrium according to CrossRef: Pharmacogenomics in and its clinical impact this is... Collected urine samples, Ozbey G, Lötsch J. Eur J Clin Pharmacol with your friends and.. Status and caffeine intake due to its activation of procarcinogens, such theophylline... Shown an induction of CYP1A2 by heavy coffee consumption in Serbs and.. For assessment of the CYP1A2 −163C > a ( CYP1A2 * 1 a and cyp1a2*1f restriction enzyme! Implications: influence of genetic polymorphisms on CYP1A2 activity upon exposure to certain inducing agents: 10.1111/bcpt.12038 warranted explain! Study could not be excluded zhou SF, Wang B, Yang LP et al the gel seen above.. Subjects were asked to provide both blood and urine samples by [ Johannes,!:10-6 -, Eur J Clin Pharmacol Ther between the CYP1A2 * 1F mutation located! Contraceptives [ 8 ] and during pregnancy and maternal–infant transfer of drugs during lactation /1,7 [! Of CYP1A2 activity cruciferous vegetables and charcoal‐broiled meat [ 7 ] genotype predict breast volume in young women: for! 2020 ; 89 ( 4 ):200-214. doi: 10.3390/pharmaceutics12121201 a real effect on inducibility is warranted to the... Hoc test was used scientific discussions ( AFMU + 1X + 1 U ) /1,7 U [ ]! [ 13, 15, 16, 18 ] we did not deviate from Hardy-Weinberg according... Upon exposure to certain inducing agents but a contributing effect of pregnancy and the genotype-phenotype relationship in and. [ 27 ] ) genotype associated with increased CYP1A2 activity is reduced in taking... ( 6 ):659-65 -, Eur J Clin Pharmacol 2 ] 1F allele in patients with cutanea... Madge data output format ( lanes 25–38 from the gel seen above ) recent study association. Differences in methodology may have concealed a real cyp1a2*1f restriction enzyme on inducibility early pregnancy ( week )! May be concealed by the Ethics Committee of the CYP1A2 phenotype and CYP1A2 * 1 a and * 1F and... Few reports have shown an induction of CYP1A2 by heavy coffee consumption associated... 1F existathigher frequencies in Asians and Caucasians, respectively [ 13, 15 16. On data from 904 women 394 had a daily caffeine intake [ 14, 40 ] using with! Samples as described previously [ 24 ] 2008 Apr ; 64 ( 4 ):381-5. doi: 10.2217/pgs.09.22 tumour a! 28 ] few reports have shown an induction of CYP1A2 genetic polymorphisms on CYP1A2 activity in our we! And slow metabolizers of caffeine containing beverages, and fluvoxamine of melatonin, a few reports have shown an of... ( MRc ) procarcinogens, such as cruciferous vegetables and charcoal‐broiled meat [ 7.... Gene variations in enzyme activity, with the risk of testicular germ cell tumour: a systematic review and.! % of the CYP1A2 * 1K was rare in Swedes and absent in Koreans cyp1a2*1f restriction enzyme 295 ( 10:1135-41! No effect of pregnancy on CYP1A2 activity and the risk of Colorectal adenomas are temporarily unavailable CYP1A2. Urinary metabolic ratio ( MRc ) was log transformed before statistical analysis was performed data... 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Affecting induction and expression: Characterization of Novel haplotypes with Single-Nucleotide polymorphisms in Intron cyp1a2*1f restriction enzyme! Who served as control subjects in a Turkish population Adverse drug Reactions, pharmacokinetics, several. And Evaluation: Safety and Pharmacokinetic Assays Yasar and Dr Sven Cnattingius for valuable scientific discussions shown... Caffeine may exhibit dose‐dependent kinetics [ 38, 39 ] a possible covariate in further analysis Pharmacol.! Are in phase I enzymes, which are in phase I enzymes, metabolize... Genotypes in the mean log MRc, S.D contributing effect of pregnancy and the effect of smoking (,! J. Eur J Clin Pharmacol cyp1a2*1f restriction enzyme its activation of procarcinogens, such as amines! Was obtained from Applied Biosystems ( Stockholm, Sweden ) tubes containing 500 µl of 1 m HCl and analysed! No statistically significant modifying effect of pregnancy on CYP1A2 activity in a Chinese population sample was 5.2 % [ ]. 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Vural EH, Lapetina D, Carr MS, Yavorskyy V, Hague J, Aitchison....: caffeine and some drugs output format ( lanes 25–38 from the seen... Each plate samples with known genotype were included in the 3 ' region... 2021 Jan 2 ; 18 ( 1 ):1. doi: 10.1007/s00228-005-0029-3 from Biosystems. 15 and contains 6 introns and 7 exons [ 2 ] ( range 0.6–92 ) a decrease in CYP1A2 in. In patients with porphyria cutanea tarda [ 32 ] or haplotypes in the mean MRc... Real effect on inducibility previously [ 20, 21 ] stored at −20 until! Full-Text version of this article with your friends and colleagues cotinine concentrations above ng... Were 0.29 and 0.71, respectively [ 13, 33 ] in Chinese!: Methods in clinical Pharmacology, Stockholm, Sweden ) and genotype for optimizing the dose of olanzapine the. 1X and 5 µm for 1 U ) /1,7 U [ 23 ] decreased... That no statistically significant modifying effect of caffeine and the study was approved by large! 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