Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes

Djordjević, Nataša; Ghotbi, Roza; Bertilsson, Leif; Janković, Slobodan; Aklillu, Eleni

doi:10.1007/s00228-007-0438-6

Cited by 95 publications

(67 citation statements)

References 22 publications

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“…In the Swedish subjects the mean age was 29 ± SD 8.3 years (range 18-60) with the mean weight 69 ± SD 12 kg (range 47-109) (no data on weight in two subjects). The Swedish subjects consisted of 112 women and 73 men and 39 (11 men and 28 women) were classified as smokers (definition of smokers > 2 cigarettes/ day) as described previously [19,20]. There were 44 women using OC.…”

Section: Study Subjectsmentioning

confidence: 99%

CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking

Ramsjö

Aklillu

Bohman

et al. 2010

Eur J Clin Pharmacol

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Objectives To compare CYP2C19 enzyme activity between Swedes and Koreans controlling for the effect of CYP2C19 genotype, sex, oral contraceptive use and smoking habit.Methods CYP2C19 activity was determined in 185 healthy Swedish and 150 Korean subjects as omeprazole/5-hydroxyomeprazole ratio (metabolic ratio; MR) using high-performance liquid chromatography. Genotyping was performed by PCR using Taqman assay.Results As expected, a higher incidence of poor metabolizers (PM) was found in Koreans (14%) compared to Swedes (3.8%) and the frequency of the CYP2C19*17 allele was very low in Koreans 0.3%. Among subjects homozygous for CYP2C19*1, Koreans displayed significantly lower CYP2C19 enzyme activity than Swedes (p<0.000001). Interestingly in Koreans a pronounced gender difference was apparent: females (n=24) had significantly lower MR than males (N=30) (p<0.0001) but such a gender difference was not seen among Swedes. Swedish OC users had a higher MR than non-users (p<0.00001), whereas OC was only used by one Korean. No effect of smoking was observed. ConclusionsWe find specific gender dependent effects of CYP2C19 activity in Koreans but not in Swedes. Controlling for the effect of genotype and sex, Koreans display lower CYP2C19 activity than Swedes. The genetic, epigenetic or environmental basis for this difference remains to be identified.

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Section: Study Subjectsmentioning

confidence: 99%

CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking

Ramsjö

Aklillu

Bohman

et al. 2010

Eur J Clin Pharmacol

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“…CYP2A6 is responsible for the hydroxylation of certain aromatic compounds such as coumarin and nicotine. 56 Two novel phosphorylation sites were located in the tryptic peptides RFpSIATLR (Ser-131) and NYpTM(Ox)SFLPR (Thr-488) ( Table 5). It has to be mentioned that RFpSIATLR is homologue in CYP2A13 and NYpTM(Ox)SFLPR is homologue in CYP2A13 and CYP2A7, although both isoforms were not unambiguously identified in any donor sample.…”

Section: Identification Of Cyp Isoforms and Phosphorylation Sites By Msmentioning

confidence: 99%

Distinction between Human Cytochrome P450 (CYP) Isoforms and Identification of New Phosphorylation Sites by Mass Spectrometry

et al. 2008

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In mammals, Cytochrome P450 (CYP) enzymes are bound to membranes of the endoplasmic reticulum and mitochondria, where they are responsible for the oxidative metabolism of many xenobiotics as well as organic endogenous compounds. In humans, 57 isoforms were identified which are classified based on sequence homology. In the present work, we demonstrate the performance of a mass spectrometry-based strategy to simultaneously detect and differentiate distinct human Cytochrome P450 (CYP) isoforms including the highly similar CYP3A4, CYP3A5, CYP3A7, as well as CYP2C8, CYP2C9, CYP2C18, CYP2C19, and CYP4F2, CYP4F3, CYP4F11, CYP4F12. Compared to commonly used immunodetection methods, mass spectrometry overcomes limitations such as low antibody specificity and offers high multiplexing possibilities. Furthermore, CYP phosphorylation, which may affect various biochemical and enzymatic properties of these enzymes, is still poorly analyzed, especially in human tissues. Using titanium dioxide resin combined with tandem mass spectrometry for phosphopeptide enrichment and sequencing, we discovered eight human P450 phosphorylation sites, seven of which were novel. The data from surgical human liver samples establish that the isoforms CYP1A2, CYP2A6, CYP2B6, CYP2E1, CYP2C8, CYP2D6, CYP3A4, CYP3A7, and CYP8B1 are phosphorylated in vivo. These results will aid in further investigation of the functional significance of protein phosphorylation for this important group of enzymes.

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“…Ethnicity is an important demographic variable affecting interindividual variability in drug metabolism and response, and a number of differences among populations have already been reported [14,24,25]. CYP2A6 exhibits marked interethnic differences [26], but data on its activity in Eastern European populations are scarce [11].…”

Section: Introductionmentioning

confidence: 99%

In vivo evaluation of CYP2A6 and xanthine oxidase enzyme activities in the Serbian population

Djordjević

Carrillo

Gervasini

et al. 2010

Eur J Clin Pharmacol

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Purpose The main aim of the study was to investigate the distribution of cytochrome P450 2A6 (CYP2A6) and xanthine oxidase (XO) enzyme activities in the Serbian population. Secondly, we tested the influence of genetics (CYP2A6 polymorphism), sex, and cigarette smoking on both enzymes. Methods One hundred forty healthy Serbian volunteers were genotyped for common CYP2A6 alleles. In 100 of them, CYP2A6 and XO activities were determined by the urinary 17U/17X and 1U/(1U+1X) ratios, respectively, after oral administration of 100 mg caffeine as a probe. Results A 21-fold variation in the 17U/17X ratio was observed (range: 0.49-10.28, mean=1.65, 95% CI: 1.49-1.83). The urinary 1U/(1U+1X) ratios displayed four-fold variation, ranging from 0.17 to 0.71 (mean=0.43, 95% CI: 0.41-0.45). CYP2A6 alleles *1A, *1B1, *9, *4 and *1B1x2 were found with frequencies of 0.579, 0.307, 0.082, 0.029, and 0.004 respectively. CYP2A6*5 was not detected. CYP2A6 genotype influenced interindividual variability in CYP2A6 enzyme activity (P=0.04). Cigarette smoking inhibited CYP2A6 enzyme activity (P=0.02), but had no effect on activity of XO (P=0.16).There was no significant difference between men and women in terms of CYP2A6 or XO activity. Conclusions Serbs displayed interindividual variations in CYP2A6 activity. CYP2A6 genotype and cigarette smoking, but not sex, influenced CYP2A6 enzyme activity. Unimodal distribution of XO enzyme activity in Serbs implies the absence of subjects with low enzyme activity in this population. XO activity is not influenced by sex or cigarette smoking.

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Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes

Abstract: Habitual heavy coffee consumption increases CYP1A2 activity. Polycyclic aromatic hydrocarbons formed during roasting of coffee beans might partly be responsible for this effect. The reason for the observed lower CYP1A2 activity in Serbs as compared to Swedes remains to be investigated.

Cited by 95 publications

References 22 publications

CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking

CYP2C19 activity comparison between Swedes and Koreans: effect of genotype, sex, oral contraceptive use, and smoking

Distinction between Human Cytochrome P450 (CYP) Isoforms and Identification of New Phosphorylation Sites by Mass Spectrometry

In vivo evaluation of CYP2A6 and xanthine oxidase enzyme activities in the Serbian population

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