Caffeine N3-demethylation (CYP1A2) in a population with an increased exposure to polychlorinated biphenyls.

Maria Skaalum Petersen, Jónrit Halling, Per Damkier, Flemming Nielsen, Philippe Grandjean, Pál Weihe, Kim Brøsen

Index: Eur. J. Clin. Pharmacol. 62(12) , 1041-8, (2006)

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Abstract

To investigate the CYP1A2 phenotype distribution in a population with an increased exposure to polychlorinated biphenyls (PCBs) that would likely induce an increased activity of this enzyme. Further, to investigate the effect of sex, smoking, and oral contraceptive use on the CYP1A2 activity.In 305 randomly selected Faroese residents aged 18-60 years, the CYP1A2 activity was determined following oral intake of a caffeine dose and subsequent determination of the urinary metabolites and calculation of the caffeine metabolic ratio (CMR). PCB exposure was assessed by measuring the serum concentration of major congeners.The CYP1A2 phenotype distribution was unimodal. The CMR was significantly higher both in smoking men and in smoking women, independent of oral contraceptive use, as compared with non-smokers. Among non-smokers, the CMR was significantly higher in women not using oral contraceptives than in those using oral contraceptives; a similar difference could not be established among smokers. The CMR appeared higher in men than in women, but stratified analyses confirmed a significant sex-related difference only among smokers not using oral contraceptives. Overall, the mean CMR in Faroese was significantly higher compared with the mean CMR in Danish historical controls. No association was found with PCB exposure and individual PCB congeners, except for one of three dioxin-like congeners, in confounder-adjusted multiple regression analyses.The CYP1A2 phenotype in Faroese residents was unimodally distributed and showed the inducing effect of smoking and the inhibiting effect of use of oral contraceptives, but a sex-related difference was not apparent after confounder adjustment. There was no statistically significant association between CMR and PCB exposure.