Pharmacogenetic screening for susceptibility to fetal malformations in women.
OBJECTIVE
To present a review of the literature and research on the pharmacogenetics of congenital defects, with a focus on the need for predictive maternal genotype assays.


METHODS
MEDLINE searches (January 1985-January 1999), past reference reviews, and unpublished research.


METHODS
Review of relevant human, animal, and basic science studies.


METHODS
Data on research on polymorphisms, genotyping, cytochrome P450 enzyme systems, epoxide hydrolase, folate metabolism, metabolism of anticonvulsant medications, molecular genetics of neural tube defects, variations in drug metabolism, and environmental exposures were evaluated.


RESULTS
Data synthesis includes not only a review of the literature but suggests ways such data might be used to facilitate the development of maternal genotype assays, with the goal of preventing birth defects.


CONCLUSIONS
Individuals vary in how they metabolize drugs and handle toxic environmental exposures. In an ideal pregnancy, there is no or limited exposure to medications and environmental agents. However, in women with chronic medical conditions such as heart disease and seizures, this is often not possible. Unfortunately, no techniques have been available to identify those at risk in this population. Gene polymorphisms for a specific enzyme may result in an absence or reduction in the level of enzyme activity or in no change at all, with little effect on the structure/function of the gene product(s); they are not associated with clinical phenotypes in either the mother or the fetus. Other polymorphisms may be only markers. Thus, developing genotyping assays for women that are predictive of phenotype expression in the fetus is the key to screening for polymorphisms. As more mutations are identified and clinical, pharmacologic, biologic, and pharmacokinetic relationships are established, using these polymorphisms to develop a genotyping assay for women may become a clinical reality, possibly leading to preventive prepregnancy or prenatal treatment that may play an increasingly effective role in maternal care.
Van Dyke
D C
DC
Children's Hospital of Iowa, University Hospital School, Iowa City 52242, USA. don-vandyke@uiowa.edu
Ellingrod
V L
VL
Berg
M J
MJ
Niebyl
J R
JR
Sherbondy
A L
AL
Trembath
D G
DG
D000013:Congenital Abnormalities / Q000175:diagnosis*; D005260:Female; D005333:Fetus / Q000002:abnormalities*; D005819:Genetic Markers; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011247:Pregnancy
D005819:Genetic Markers