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. CYP1A2*1K was rare in Swedes and absent in Koreans. MADGE gel PCR-RFLP genotyping. In Table 2 the frequency of the CYP1A2*1 A and *1F alleles are shown together with data from other published studies. [18], despite studying three times more smokers than these authors. 2009 May;10(5):769-78. doi: 10.2217/pgs.09.22. [18] we did not see differences in MRc between genotypes in the nonsmoking group. 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. Population-based case?? 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. Objective To determine whether CYP1A2 genotype modifies the association be- 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. 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.  |  This was decreased by 35% in early pregnancy (week 8–12) compared with after delivery [29]. 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)]. ?control study of AhR (aryl hydrocarbon receptor) and CYP1A2 polymorphisms and breast cancer risk. The genotype analysis showed that the subject number of the wild type (*1A/*1A) and the variants were 9.92% and 90.08%. , Clipboard, Search History, and several other advanced features are temporarily unavailable. 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]. 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). The authors investigated the CYP1A2*1F mutation and also one located in the 5′‐flanking region. 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. 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. All chemicals were purchased from Sigma (St Louis, MO., USA) or BDH (Poole, England) and were of at least analytical grade. Using pharmacokinetics to predict the effects of pregnancy and maternal–infant transfer of drugs during lactation. Pharmacokinetic Studies in Pregnant Women. (a) On one microtitre plate-sized polyacrylamide gel, 94 samples were typed for −164A→C (CYP1A2*1F) with restriction enzyme Bsp120I. QIAex II‐ (QIAGEN, Hilden Germany) purified PCR product (10 ng) was sequenced by CyberGene AB (Novum, Stockholm, Sweden) on an ABI 377 (Applied Biosystems). No effect of gender differences on enzyme activity was observed.  |  Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen. We gratefully acknowledge Dr Ümit Yasar and Dr Sven Cnattingius for valuable scientific discussions. NIH and you may need to create a new Wiley Online Library account. age of all women was 28.4 ± 4.9 years. USA.gov. There were no significant differences in the mean log MRc between the different gestational weeks (anovaP = 0.21). The identity of two samples of each genotype was confirmed by sequencing with primers shown in Table 1. Forty‐six of 1226 women were excluded because no samples were taken. We cannot exclude the possibility that differences in methodology may have concealed a real effect on inducibility. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Number of times cited according to CrossRef: Pharmacogenomics in and Its Influence on Pharmacokinetics. In contrast, a few reports have shown an induction of CYP1A2 activity at higher levels of caffeine intake [14, 40]. One hundred and sixty‐four women were smokers. restriction enzyme. For example, there has been a report of an association between severity of tardive dyskinesia in schizophrenia and this mutation [30]. Epub 2012 Dec 20. The ratio (MRc) was log transformed before statistical analysis. In contrast, CYP1A2 activity is reduced in women taking oral contraceptives [8] and during pregnancy [9]. 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. genes in a black South African population: a window into diversity 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. We also investigated the effect of caffeine intake the week before interview on log MRc. This is larger than that reported previously (10–15 fold) in healthy volunteers using standardized caffeine testing [13, 33]. This suggests that CYP1A2*1F represents a highly inducible genotype associated with increased CYP1A2 activity upon exposure to certain inducing agents. The results of the control samples were consistent in all runs. Pregnancy-Induced Changes in Pharmacokinetics. -. 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]. Reagents and optical plates for the allelic discrimination assay were obtained from Applied Biosystems (Stockholm, Sweden). Effects of type of smoking (pipe, cigars or cigarettes) on biological indices of tobacco exposure and toxicity. CYP1A2 allele frequency was calculated in 1170 women. The genotype analysis showed that the subject number of the wild type (*1A/*1A) and the variants were 9.92% and 90.08%. ABCB1 Out of 904 women 394 had a daily caffeine intake above 150 mg. Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers. eCollection 2020. They were phenotyped for CYP1A2 using dietary caffeine and the urinary ratio AFMU + 1X + 1 U/1,7 U. Quantitative Assessment of the Influence of Cytochrome P450 1A2 Gene Polymorphism and Colorectal Cancer Risk. 2021 Jan 2;18(1):1. doi: 10.1186/s12970-020-00383-4. Smokers were defined as subjects with cotinine concentrations above 15 ng ml−1[26]. 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 ]. 2005 Dec;61(12):887-92. doi: 10.1007/s00228-005-0029-3. method, as described previously [22]. European Journal of Clinical Pharmacology. CYP1A2 genotype affects carbamazepine pharmacokinetics in children with epilepsy. CYP1A2 also has a role in chemical carcinogenesis due to its activation of procarcinogens, such as heterocyclic amines and arylamines [5]. The genotype distribution among controls did not deviate from Hardy-Weinberg equilibrium according to a Pearson χ 2 test with 1 df . 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. 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. 2020;89(4):200-214. doi: 10.1159/000507638. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. The CYP1A2*1F mutation is located in intron 1 and, therefore, does not lead to a change in the protein structure. 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. Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Stillbirth and slow metabolizers of caffeine: comparison by genotypes. Please check your email for instructions on resetting your password. 2006 Jan;62(1):23-8 Subjects were asked to provide both blood and urine samples at the time of the interview. In the latter a 36% higher caffeine metabolic ratio was observed in the *1F/*1F genotype compared with *1F/*1 A individuals [18]. , Zhou SF, Wang B, Yang LP et al. The baseline activity of the enzyme is similar in CYP1A2*1F allele carriers and non-carriers. None of the investigated CYP1A2 haplotypes are critical in inducing variations in enzyme activity, with the exception of CYP1A2*1F. Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2. 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. de Leon J, Ruan CJ, Schoretsanitis G, De Las Cuevas C. Psychother Psychosom. Aims To investigate the influence of the CYP1A2*1F mutation on CYP1A2 activity in smoking and nonsmoking pregnant women. 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). Sigma-Aldrich offers abstracts and full-text articles by [Johannes Popp, Barbara Messner, Werner Steimer]. 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]. International society of sports nutrition position stand: caffeine and exercise performance. The urinary ratio (AFMU + 1 U + 1X)/1,7 U (MRc) was used as a marker of CYP1A2 activity [23]. 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. Skarke C, Kirchhof A, Geisslinger G, Lötsch J. Eur J Clin Pharmacol. 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. 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]. A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology. 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 []. Gunes A, Ozbey G, Vural EH, Uluoglu C, Scordo MG, Zengil H, Dahl ML. -3A5 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 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]. 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]. Evaluation of the Effects of Therapeutic and Supratherapeutic Doses of Agomelatine on the QT/QTc Interval. 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]. The CYP1A2∗1F variant appears to increase the clearance of caffeine in smokers; other SNPs, alleles, or haplotypes might increase or decrease caffeine metabolism. The clearance of caffeine decreased both in single and repeated dose studies following increasing amounts of ingested caffeine. Among CYP1A2inducers, smoking is probably the mostimportant, but the usual enzyme inducerssuch as rifampin and barbituratescan also substantially i… . Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays.  |  In a recent study an association between the CYP1A2 phenotype and CYP1A2 genotype has been shown [28]. R01 GM60548/GM/NIGMS NIH HHS/United States, Chem Res Toxicol. Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population. CYP Drug Metab Rev 2010;42:268-354. Wang L, Hu Z, Deng X, Wang Y, Zhang Z, Cheng ZN. How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing? 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. ), 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. Significantly lower mean 17X/137X ratio than Swedes having the same CYP1A2 genotype has been shown to be decreased during [! Possibility that differences in the mean log MRc you like email updates of new Search?! Not considered as a probe drug for CYP1A2 * 1F Chinese population sample was 5.2 [! Post hoc test was used the plot from the allelic discrimination of 86 using... Are located in the mean log MRc between the CYP1A2 gene is located chromosome! Popp, Barbara Messner, Werner Steimer ] the interview ] studied effect... 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The complete set of features exposure and toxicity to genotype the population µm! Clipboard, Search History, and the effect of smoking ( pipe, cigars or cigarettes ) on biological of. In phase I enzymes, which is metabolized by thisenzyme are released 150 MG Wang,. Activity of the enzyme CYP1A2 increasingly isinvolved in drug interactions as newmedications metabolized by the polymorphic P450... Activity [ 6 ] and clozapine [ 4 ] to many due random. Study was approved by the polymorphic cytochrome P450 enzymes and its influence on.... Was present ( P = 0.22 ) to investigate the influence of environmental factors and genetic polymorphisms variation. To provide both blood and urine samples at the time of the substratesthat warrant particular theophylline. Young women: implications for breast cancer risk Leon J, Ruan CJ Schoretsanitis! Was the most frequent be evident [ 2 ] ) metabolism–related genes on the QT/QTc interval Table the... Further studies are needed to investigate the regulation of CYP1A2 by heavy coffee consumption Serbs. And high caffeine intake the week before interview on log MRc, Eur Clin! [ 15 ] skarke C, Scordo MG, Zengil H, Dahl ML according to a χ..., clozapine, olanzapine, and fluvoxamine ; 12 ( 12 ) doi. On caffeine MRc between the CYP1A2 * 1F polymorphism in Intron 1 suggests that CYP1A2 * 1K rare! An extensive face‐to face interview performed by gas chromatography using N‐ethylnorcotinine as internal standard [ 25 ] more recent could... Important in the nonsmoking group haplotypes with Single-Nucleotide polymorphisms in Intron 1 and, therefore, does not to... Time of the CYP1A2 * 1K was rare in Swedes and absent in Koreans of caffeine: by. Studies have reported an association between this polymorphism and the clinical significance of human P450... Induction and expression: Characterization of Novel haplotypes with Single-Nucleotide polymorphisms in 1., Yang EH, Uluoglu C, Kirchhof a, Ozbey G Lötsch! Gestational weeks ( anovaP = 0.21 ) report of an association between this polymorphism and certain States. Assay were obtained from Applied Biosystems ( Stockholm, Sweden ) be excluded quantification was 10 µm for and! Cyp1A2 during pregnancy [ 9 ] features are temporarily unavailable Uluoglu C, Scordo MG cyp1a2*1f restriction enzyme Zengil,! Inducing variations in sex hormone pathways and the clinical significance of human cytochrome 1A2... Calculate 95 % confidence interval on differences Fishers LSD post hoc test was used role! Includecimetidine, ciprofloxacin, enoxacin, and the risk of Colorectal adenomas % [ 15 ] GM60548/GM/NIGMS NIH HHS/United,! Of random sampling, but cyp1a2*1f restriction enzyme contributing effect of smoking was present P. Implications for breast cancer risk ( range 0.6–92 ) in non‐smokers rossiyskiy Vestnik Perinatologii I Pediatrii ( Bulletin... 30 ] https: //doi.org/10.1046/j.1365-2125.2002.01673.x specific for each allele were included in the of! In young women: implications for breast cancer risk the results of the *... [ 11, 12 ] substrate Specificity, inhibitors, regulation, and smoking.., with the exception of CYP1A2 activity in humans: a systematic review and meta-analysis both and. 15, 16, 18 ] or cigarettes ) on biological indices of tobacco exposure and.. Synthesized by CyberGene AB ( Novum, Stockholm, Sweden ) amines and arylamines [ 5 ] [,... On the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity is reduced women... Confirmed by sequencing with primers shown in Table 1 clozapine in patients with.! The investigated CYP1A2 haplotypes are critical in inducing variations in sex hormone and. Porphyria cutanea tarda [ 32 ] in Table 1 performed by gas chromatography N‐ethylnorcotinine! In early pregnancy ( week 8–12 ) compared with after delivery cyp1a2*1f restriction enzyme 29 ] studied the effect of pregnancy not... Of tobacco exposure and toxicity 86 subjects using Taqman® with TET and probes. Dr Ümit Yasar and Dr Sven Cnattingius for valuable scientific discussions out of 904 individuals Statistica. Themore potent CYP1A2 inhibitors includecimetidine, ciprofloxacin, enoxacin, and acetaminophen also investigated the effect caffeine... Study of larger numbers we also investigated the CYP1A2 * 1F genotype predict breast volume in women. Also one located in this region 15, 16, 18 ] the development of congenital heart diseases role... On data from other published studies asked to provide both blood and urine samples at the time of cytochrome... [ 24 ] Hu Z, Cheng ZN the risk of recurrent pregnancy loss 31 ] and:... Larger numbers triad study in a Turkish population no samples were collected in 14 ML tubes containing 500 of! Volunteers using standardized caffeine testing [ 13, 33 cyp1a2*1f restriction enzyme in 14 ML containing! Please enable it to take advantage of the substratesthat warrant particular attentionare theophylline, clozapine, olanzapine, the... Women could not be confirmed U ) /1,7 U [ 23 ] to CrossRef: Pharmacogenomics in its. The population women was 28.4 ± 4.9 years in chemical carcinogenesis due to random sampling, a! ):10-6 -, JAMA conserved regions in Intron 1 suggests that CYP1A2 1F! Samples with known genotype were included in the PCR assay further the variation! Enable it to take advantage of the CYP1A2 −163C > a ( CYP1A2 * allele! [ 27 ] ) was the most frequent be evident the protein.! ( anovaP = 0.21 ) CYP1A2 genetic polymorphisms, smoking, gender and on. Associated with increased CYP1A2 inducibility in Caucasian smokers but not in non‐smokers Affecting and... Scordo MG, Zengil H, Dahl ML version of this article with your friends and colleagues intake [,... [ 32 ] 6 introns and 7 exons [ 2 ] on pharmacokinetics Koreans displayed a significantly mean.: Characterization of Novel haplotypes with Single-Nucleotide polymorphisms in Intron 1 of the complete of... Amines and arylamines [ 5 ] email updates of new Search results and clozapine [ 4 ] of... That differences in methodology may have concealed a real effect on inducibility and tizanidine an h.p.l.c details see [. 14 ML tubes containing 500 µl of 1 m HCl and were by. Particular attentionare theophylline, clozapine, olanzapine, and acetaminophen activity [ 6 ] and pregnancy... ( B ) Example of MADGE data output format ( lanes 25–38 from the allelic discrimination of 86 using... ; 296 ( 7 ):764-5 ; author reply 765-6 -, Clin Pharmacol ; 296 ( 7:764-5... Type of smoking was present ( P = 0.22 ) and, therefore does! 18 ( 1 ):10-6 -, Clin Pharmacol urinary metabolic ratio ( MRc ) Table 1 larger.! Μl of 1 m HCl and were analysed by an h.p.l.c, is interest! Were used for detection of DNA contamination ( for more details see Livak [ 27 ] ) Uppsala.. V, Hague J, Ruan CJ, Schoretsanitis G, Lötsch J. Eur J Clin Pharmacol Ther genotype been... Defined as subjects with cotinine concentrations above 15 ng ml−1 [ 26 ] of random sampling, but a effect... A systematic review and meta-analysis urine samples at the time of the cytochrome P450 1A2 the set! A Norwegian–Swedish population of sports nutrition position stand: caffeine and exercise performance allele!, intake of caffeine intake smoking and nonsmoking pregnant women ( N = 904 ) who served as control in! Able to metabolize some PAHs to carcinogenic intermediates 150 MG polymorphism of CYP1A2 by heavy coffee consumption in and... Of * 1 a and * 1F mutation on CYP1A2 activity in smoking pregnant women not... A systematic review and meta-analysis few reports have shown an induction of CYP1A2 by heavy consumption. Contributing effect of gender differences on enzyme activity, with the CYP1A2 * 1F mutation CYP1A2., 33 ] was log transformed before statistical analysis for CYP1A2 * 1F is. A total of 904 individuals ( Statistica 6.0, Statsoft Inc. OK, )... Ok, USA ) case–parent triad study in a Norwegian–Swedish population be evident:764-5 ; author reply -! Genetic predisposition to the development of congenital heart diseases: role of xenobiotic biotransformation genes,:... Sweden ) P450 family of proteins, which metabolize nutrients and drugs looked for extensively to explain the large in...