A literature review was performed to collect information on the role of pharmacogenetics in six proposed teratogenic mechanisms associated with drug use during pregnancy: folate antagonism, oxidative stress, angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism, cyclooxygenase-1 and -2 inhibition, 5-hydroxytryptamine-reuptake inhibition and drug transporters in the placenta. Data on the direct relationship between pharmacogenetics and drug-induced birth defects were found for folate metabolism, oxidative stress caused by phenytoin exposure and drug transporters in the placenta. Although no specific data to support pharmacogenetic-related birth defects were found for the NSAIDs, paroxetine and fluoxetine, it might be expected that polymorphisms modify their teratogenic effects. The usually low prevalence of drug-induced malformations impedes the demonstration of the contribution of pharmacogenetics. Large-scale studies, preferably case-control studies, are needed.
Serotonin as a regulator of craniofacial morphogenesis: site specific malformations following exposure to serotonin uptake inhibitors
Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group
An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels
Identification, expression, and pharmacology of a Cys23-Ser23 substitution in the human 5-HT2c receptor gene (HTR2C)
Assignment of the 36.5-kDa (RFC5), 37-kDa (RFC4), 38-kDa (RFC3), and 40-kDa (RFC2) subunit genes of human replication factor C to chromosome bands 12q24.2-q24.3, 3q27, 13q12.3-q13, and 7q11.23
In vivo phenytoin-initiated oxidative damage to proteins and lipids in murine maternal hepatic and embryonic tissue organelles: potential molecular targets of chemical teratogenesis
Oxygen-induced embryopathy and the significance of glutathione-dependent antioxidant system in the rat embryo during early organogenesis
Are common mutations of cystathionine beta-synthase involved in the aetiology of neural tube defects?
Sequence analysis of the coding region of human methionine synthase: relevance to hyperhomocysteinaemia in neural-tube defects and vascular disease
Screening of the C677T mutation on the methylenetetrahydrofolate reductase gene in French patients with neural tube defects
Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors: a prospective controlled multicenter study
A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?
Molecular genetic analysis of the gene encoding the trifunctional enzyme MTHFD (methylenetetrahydrofolate-dehydrogenase, methenyltetrahydrofolate-cyclohydrolase, formyltetrahydrofolate synthetase) in patients with neural tube defects
Placental P-glycoprotein deficiency enhances susceptibility to chemically induced birth defects in mice
Teratogenicity of the class III antiarrhythmic drug almokalant. Role of hypoxia and reactive oxygen species
Genetic polymorphisms in methylenetetrahydrofolate reductase and methionine synthase, folate levels in red blood cells, and risk of neural tube defects
Analysis of select folate pathway genes, PAX3, and human T in a Midwestern neural tube defect population
A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida
HTR2C Cys23Ser polymorphism in relation to CSF monoamine metabolite concentrations and DSM-III-R psychiatric diagnoses
Possible interaction of genotypes at cystathionine beta-synthase and methylenetetrahydrofolate reductase (MTHFR) in neural tube defects. NTD Collaborative Group
Linkage disequilibrium of MTHFR genotypes 677C/T-1298A/C in the German population and association studies in probands with neural tube defects(NTD)
Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention
Angiotensin II type 1 receptor A1166C gene polymorphism is associated with an increased response to angiotensin II in human arteries
The thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) is not a major risk factor for neural tube defect in American Caucasians. The NTD Collaborative Group
Altered folate metabolism and disposition in mothers affected by a spina bifida pregnancy: influence of 677c --> t methylenetetrahydrofolate reductase and 2756a --> g methionine synthase genotypes
Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study
Interaction of folate and homocysteine pathway genotypes evaluated in susceptibility to neural tube defects (NTD) in a German population
Analysis of the EPHX1 113 polymorphism and GSTM1 homozygous null polymorphism and oral clefting associated with maternal smoking
Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark
Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.