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Mol. Hum. Reprod. Advance Access published online on April 22, 2005
Molecular Human Reproduction, doi:10.1093/molehr/gah175
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Molecular Human Reproduction © The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received February 28, 2005
Accepted April 4, 2005

Article

Caffeine intake, CYP1A2 polymorphism and the risk of recurrent pregnancy loss

Fumihiro Sata 1*, Hideto Yamada 2, Kana Suzuki 1, Yasuaki Saijo 1, Emi H Kato 2, Mamoru Morikawa 2, Hisanori Minakami 2, and Reiko Kishi 1

1 Department of Public Heath, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan and
2 Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo 060-8638, Japan

* To whom correspondence should be addressed.
Fumihiro Sata, E-mail: fsata{at}med.hokudai.ac.jp


  Abstract

Some case-control studies have demonstrated that caffeine intake and high CYP1A2 activity increase risks of recurrent pregnancy loss (RPL) but the multifactorial effect is obscure. To investigate whether susceptible women who have more caffeine intake are at high risk of RPL, a case-control study of 58 cases with two or more RPL and fertile 147 controls was performed. The association between daily caffeine intake together with CYP1A2*1F (AA versus CA and CC) genotype and RPL was assessed. Without consideration of the genotype, there were no significant differences of the RPL risk in proportion to daily caffeine intake [less than 100 mg (reference); 100-299 mg: odds ratio (OR), 1.29; 95% confidence interval (CI), 0.66-2.50; 300 mg or more: OR, 1.82; 95% CI, 0.72-4.58; P for trend, 0.20]. However, the RPL risk significantly increased only among women who had homozygous CYP1A2*1F alleles with a dosage effect of daily caffeine intake [less than 100 mg (reference); 100-299 mg: OR, 1.94; 95% CI, 0.57-6.66; 300 mg or more: OR, 5.23; 95% CI, 1.05-25.9; P for trend, 0.03]. It was demonstrated for the first time that an increase in caffeine intake deteriorates the fecundity among susceptible women.

Keywords: caffeine; CYP1A2; genetic polymorphism; molecular epidemiology; recurrent pregnancy loss.
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