Premium
The effect of the CYP1A2 *1F mutation on CYP1A2 inducibility in pregnant women
Author(s) -
Nordmark Anna,
Lundgren Stefan,
Ask Birgitta,
Granath Fredrik,
Rane Anders
Publication year - 2002
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2002.01673.x
Subject(s) - cyp1a2 , confidence interval , genotype , caffeine , analysis of variance , medicine , heterozygote advantage , allele , population , urine , endocrinology , biology , genetics , metabolism , environmental health , cytochrome p450 , gene
Aims To investigate the influence of the CYP1A2 * 1F mutation on CYP1A2 activity in smoking and nonsmoking pregnant women.Methods Pregnant women ( n = 904) who served as control subjects in a case‐control study of early fetal loss were investigated. They were phenotyped for CYP1A2 using dietary caffeine and the urinary ratio AFMU + 1X + 1 U/1,7 U. An assay for CYP1A2 * 1F using 5′‐nuclease assay (Taqman) was developed to genotype the population. Results The frequencies of * 1 A and * 1F alleles among Swedish women were 0.29 and 0.71, respectively. There was no statistically significant difference in CYP1A2 activity between the genotypes, although a trend towards enhanced activity was observed in * 1F / * 1F (log MR c 0.77) and * 1F/ * 1 A (log MR c 0.82) genotypes compared with the * 1 A/ * 1 A genotype (log MR c 0.71) ( anova P = 0.07). 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)]. 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 MR c 0.79, * 1F/ * 1 A log MR c 0.86, and * 1 A/ * 1 A log MR c 0.73). 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]. Conclusions The effect of the CYP1A2 * 1F mutation on CYP1A2 activity in smoking pregnant women could not be confirmed.