Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers

This study was designed to investigate the impact of cytochrome P450 (CYP) 1A2 polymorphisms on theophylline metabolism in a non‐smoking healthy male Chinese population. Four polymorphisms CYP1A2*1C (G‐3860A), G‐3113A, CYP1A2*1F (C‐163A) and CYP1A2*1B (C‐5347T) were screened in 238 unrelated male vo...

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Published in:Basic & clinical pharmacology & toxicology 2013-04, Vol.112 (4), p.257-263
Main Authors: Wang, Liqing, Hu, Zheyi, Deng, Xun, Wang, Yong, Zhang, Zhongyi, Cheng, Ze‐Neng
Format: Article
Language:English
Subjects:
Adolescent
Asian Continental Ancestry Group
Caffeine - metabolism
China
Chromatography, High Pressure Liquid
Cytochrome P-450 CYP1A2 - genetics
Genotype
Haplotypes
Humans
Male
Polymorphism, Single Nucleotide
Theophylline - blood
Theophylline - metabolism
Young Adult
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creator Wang, Liqing
Hu, Zheyi
Deng, Xun
Wang, Yong
Zhang, Zhongyi
Cheng, Ze‐Neng
description This study was designed to investigate the impact of cytochrome P450 (CYP) 1A2 polymorphisms on theophylline metabolism in a non‐smoking healthy male Chinese population. Four polymorphisms CYP1A2*1C (G‐3860A), G‐3113A, CYP1A2*1F (C‐163A) and CYP1A2*1B (C‐5347T) were screened in 238 unrelated male volunteers. Then, a single oral 200‐mg dose of theophylline was administered to 37 volunteers, who were selected from 238 volunteers based on the CYP1A2 genotype. CYP1A2 activities were evaluated by plasma 1,7‐dimethylxanthine/caffeine ratios (17X/137X) after administration of 100‐mg caffeine. The plasma concentrations of theophylline, 17X and 137X were determined by high‐performance liquid chromatography. The activity of CYP1A2 was lower in volunteers with the ‐3113 AA genotype compared with those with the ‐3113 AG genotype (0.35 ± 0.04 versus 0.48 ± 0.07, p = 0.016) or the ‐3113 GG genotype (0.35 ± 0.04 versus 0.58 ± 0.22, p = 0.037). CYP1A2*1F polymorphisms were associated with increased CYP1A2 activity in volunteers with ‐3860G/‐3113G/5347C homozygosity (0.66 ± 0.24 versus 0.46 ± 0.05, p = 0.034). However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. CYP1A2 genetic polymorphisms influenced CYP1A2 enzyme activity as measured by caffeine, but CYP1A2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study.
doi_str_mv 10.1111/bcpt.12038
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However, theophylline metabolism showed no difference among volunteers carrying different haplotype pairs. CYP1A2 genetic polymorphisms influenced CYP1A2 enzyme activity as measured by caffeine, but CYP1A2 gene polymorphisms appeared to have limited influence on theophylline metabolism in our study.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>23167834</pmid><doi>10.1111/bcpt.12038</doi><tpages>7</tpages></addata></record>
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subjects Adolescent
Asian Continental Ancestry Group
Caffeine - metabolism
China
Chromatography, High Pressure Liquid
Cytochrome P-450 CYP1A2 - genetics
Genotype
Haplotypes
Humans
Male
Polymorphism, Single Nucleotide
Theophylline - blood
Theophylline - metabolism
Young Adult
title Association between Common CYP1A2 Polymorphisms and Theophylline Metabolism in Non‐smoking Healthy Volunteers
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