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Stillbirth and slow metabolizers of caffeine: comparison by genotypes.
Int J Epidemiol. 2006 Aug; 35(4):948-53.IJ

Abstract

BACKGROUND

Cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) are key enzymes in the metabolism of caffeine. The polymorphism of these genes facilitates the detection of fast and slow metabolizers, and if caffeine is causally related to stillbirth, we expect slow metabolizers to have a higher risk of stillbirth at any given intake of caffeine. Gluthatione S-transferase alpha1 (GSTA1) may also be active in the metabolism of caffeine as it conjugates glutathione to aromatic amines. Our study, therefore, included analyses of the association between GSTA1 and stillbirth.

METHODS

A nested case non-case study among women who participated in the Danish National Birth Cohort: 142 cases of singleton stillbirths and 157 controls of singleton live births.

RESULTS

Slow oxidizer status (CYP1A2), slow acetylator status (NAT2), and low activity of GSTA1 were not individually associated with the risk of stillbirth [odds ratio (OR) = 1.06, 95% confidence interval (95% CI) 0.67-1.67, OR = 0.95, 95% CI 0.60-1.51, and OR = 1.42, 95% CI 0.88-2.28, respectively]. We did, however, observe that subjects with a combination of slow CYP1A2, slow NAT2, and low GSTA1 genes had almost a 2-fold risk of stillbirth compared with subjects with other combinations of genotypes.

CONCLUSIONS

We found no link between any single genotype and the risk of stillbirth. An association between a combination of genotypes and stillbirth was discovered. Caffeine may be causally related to stillbirth, but larger studies using Mendelian randomization are needed to verify this.

Authors+Show Affiliations

The Danish Epidemiology Science Centre, Department of Epidemiology, Institute of Public Health, University of Aarhus, 8000 Aarhus, Denmark. bhb@soci.au.dkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16782969

Citation

Bech, Bodil Hammer, et al. "Stillbirth and Slow Metabolizers of Caffeine: Comparison By Genotypes." International Journal of Epidemiology, vol. 35, no. 4, 2006, pp. 948-53.
Bech BH, Autrup H, Nohr EA, et al. Stillbirth and slow metabolizers of caffeine: comparison by genotypes. Int J Epidemiol. 2006;35(4):948-53.
Bech, B. H., Autrup, H., Nohr, E. A., Henriksen, T. B., & Olsen, J. (2006). Stillbirth and slow metabolizers of caffeine: comparison by genotypes. International Journal of Epidemiology, 35(4), 948-53.
Bech BH, et al. Stillbirth and Slow Metabolizers of Caffeine: Comparison By Genotypes. Int J Epidemiol. 2006;35(4):948-53. PubMed PMID: 16782969.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stillbirth and slow metabolizers of caffeine: comparison by genotypes. AU - Bech,Bodil Hammer, AU - Autrup,Herman, AU - Nohr,Ellen Aagaard, AU - Henriksen,Tine Brink, AU - Olsen,Jørn, Y1 - 2006/06/16/ PY - 2006/6/20/pubmed PY - 2007/7/14/medline PY - 2006/6/20/entrez SP - 948 EP - 53 JF - International journal of epidemiology JO - Int J Epidemiol VL - 35 IS - 4 N2 - BACKGROUND: Cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) are key enzymes in the metabolism of caffeine. The polymorphism of these genes facilitates the detection of fast and slow metabolizers, and if caffeine is causally related to stillbirth, we expect slow metabolizers to have a higher risk of stillbirth at any given intake of caffeine. Gluthatione S-transferase alpha1 (GSTA1) may also be active in the metabolism of caffeine as it conjugates glutathione to aromatic amines. Our study, therefore, included analyses of the association between GSTA1 and stillbirth. METHODS: A nested case non-case study among women who participated in the Danish National Birth Cohort: 142 cases of singleton stillbirths and 157 controls of singleton live births. RESULTS: Slow oxidizer status (CYP1A2), slow acetylator status (NAT2), and low activity of GSTA1 were not individually associated with the risk of stillbirth [odds ratio (OR) = 1.06, 95% confidence interval (95% CI) 0.67-1.67, OR = 0.95, 95% CI 0.60-1.51, and OR = 1.42, 95% CI 0.88-2.28, respectively]. We did, however, observe that subjects with a combination of slow CYP1A2, slow NAT2, and low GSTA1 genes had almost a 2-fold risk of stillbirth compared with subjects with other combinations of genotypes. CONCLUSIONS: We found no link between any single genotype and the risk of stillbirth. An association between a combination of genotypes and stillbirth was discovered. Caffeine may be causally related to stillbirth, but larger studies using Mendelian randomization are needed to verify this. SN - 0300-5771 UR - https://www.unboundmedicine.com/medline/citation/16782969/Stillbirth_and_slow_metabolizers_of_caffeine:_comparison_by_genotypes_ L2 - https://academic.oup.com/ije/article-lookup/doi/10.1093/ije/dyl116 DB - PRIME DP - Unbound Medicine ER -