The effect of the CYP1A2 *1F mutation on CYP1A2 inducibility in pregnant women.
OBJECTIVE
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 MRc 0.77) and *1F/*1 A (log MRc 0.82) genotypes compared with the *1 A/*1 A genotype (log MRc 0.71) (anovaP = 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 MRc 0.79, *1F/*1 A log MRc 0.86, and *1 A/*1 A log MRc 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.
Nordmark
Anna
A
Department of Medical Laboratory Science and Technology, Division of Clinical Pharmacology, Karolinska Institutet, C-168, Huddinge University Hospital, SE-141 86 Stockholm, Sweden. anna.nordmark@labtek.ki.se
Lundgren
Stefan
S
Ask
Birgitta
B
Granath
Fredrik
F
Rane
Anders
A
D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy / Q000235:genetics*; D012907:Smoking / Q000235:genetics*
D019388:Cytochrome P-450 CYP1A2