Induction of CYP1A2 by heavy coffee consumption is associated with the CYP1A2 -163C>A polymorphism.
OBJECTIVE
To investigate the association of CYP1A2 genetic polymorphisms with the inducing effect of heavy coffee consumption on CYP1A2 activity in Serbian and Swedish populations, and to determine the frequency of the CYP1A2 genetic polymorphisms in Serbs.


METHODS
Using PCR-RFLP and the tag-array minisequencing method, 126 Serbian healthy volunteers were genotyped for -3860G>A, -2467delT, -739T>G, -729C>T, -163C>A, 2159G>A, and 4795G>A. For 64 nonsmoking participants, the data on CYP1A2 activity (plasma paraxanthine/caffeine ratio) and coffee consumption habit were available from our previous study. The data on CYP1A2 genotype, enzyme activity, and coffee consumption from 114 Swedish healthy nonsmoking subjects were included in the analyses.


RESULTS
In Serbs, CYP1A2 polymorphisms -3860G>A, -2467delT, -739T>G, -729C>T, -163C>A, and 2159G>A were found at the frequencies of 0.4, 5.0, 3.4, 0.7, 61.1, and 56.0%, respectively, while 4795G>A was not detected. Significant association of heavy coffee consumption with high CYP1A2 enzyme activity was observed only in carriers of -163 A/A. Increasing effect of -163C>A on CYP1A2 inducibility was found in both Serbian (P=0.022) and Swedish (P=0.016) nonsmoking heavy coffee consumers. There was no significant difference in CYP1A2 enzyme activity among genotypes in non-heavy coffee consumers. The results indicate that 22 and 14% of the phenotypic variability among Serbian and Swedish heavy coffee consumers, respectively, might be explained by -163C>A polymorphism.


CONCLUSIONS
CYP1A2 polymorphism -163C>A has an important increasing effect on CYP1A2 inducibility by heavy coffee consumption and may possibly be a contributing factor for interindividual variations in CYP1A2 enzyme activity.
Djordjevic
Natasa
N
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, C1: 68 SE-141 86 Stockholm, Sweden.
Ghotbi
Roza
R
Jankovic
Slobodan
S
Aklillu
Eleni
E
D003069:Coffee / Q000009:adverse effects*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis* / Q000235:genetics*; D004790:Enzyme Induction / Q000187:drug effects*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D055771:Serbia; D013548:Sweden; D044465:White People / Q000235:genetics
D003069:Coffee; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2
Pharmacogenetics. 1994 Jun;4(3):109-16
7920690
Br J Clin Pharmacol. 2002 Nov;54(5):540-3
12445035
J Biochem. 1999 Apr;125(4):803-8
10101295
Clin Pharmacol Ther. 1998 May;63(5):540-51
9630827
Br J Clin Pharmacol. 1999 Apr;47(4):445-9
10233211
Nucleic Acids Res. 2002 Jul 15;30(14):e70
12136118
Prog Neuropsychopharmacol Biol Psychiatry. 2002 Feb;26(2):261-5
11817502
Mol Pharmacol. 2003 Sep;64(3):659-69
12920202
Br J Clin Pharmacol. 2002 Nov;54(5):504-10
12445029
Ann Clin Biochem. 2005 May;42(Pt 3):216-9
15949157
Eur J Clin Pharmacol. 2010 Jun;66(6):571-8
20155256
Eur J Clin Pharmacol. 1985;28(4):425-8
4029248
Hum Mutat. 2001 Apr;17(4):355-6
11295848
J Hypertens. 2009 Aug;27(8):1594-601
19451835
Pharmacogenomics. 2009 May;10(5):769-78
19450128
Eur J Clin Pharmacol. 2007 Jun;63(6):537-46
17370067
Jpn J Cancer Res. 1999 Sep;90(9):899-902
10551315
Eur J Clin Pharmacol. 2006 Jan;62(1):23-8
16385402
Clin Pharmacol Ther. 1991 Jan;49(1):44-8
1988240
Drug Metab Rev. 2010 May;42(2):268-354
19961320
Antimicrob Agents Chemother. 1992 May;36(5):942-8
1510417
Cancer Epidemiol Biomarkers Prev. 1994 Jul-Aug;3(5):413-21
7920209
J Chromatogr B Biomed Sci Appl. 1998 May 8;709(1):27-34
9653923
Mutat Res. 2005 Nov 10;587(1-2):59-66
16188490
Cancer Epidemiol Biomarkers Prev. 2008 Apr;17(4):895-901
18398030
Eur J Clin Pharmacol. 2008 Apr;64(4):381-5
18157525
Clin Pharmacol Ther. 2007 Feb;81(2):270-83
17259951
Br J Clin Pharmacol. 1998 Feb;45(2):176-8
9491835
Br J Clin Pharmacol. 2003 Jan;55(1):68-76
12534642