Genetic polymorphisms in placental transporters: implications for fetal drug exposure to oral antidiabetic agents.
BACKGROUND
The prevalence of diabetes among women of childbearing age is increasing. This will inevitably increase the number of pregnancies complicated by diabetes. The management of diabetes mellitus often necessitates the use of oral antidiabetic drugs including biguanides, sulfonylureas, metiglinide analogs and thiazolidinediones. However, a significant concern with the use of these agents in pregnancy is the potential for developmental toxicity. Various antidiabetic drugs have been identified as substrates for transporters present in the syncytiotrophoblast. Therefore, the extent of transfer and fetal exposure to oral antidiabetic drugs used in pregnancy may be altered by polymorphisms in genes encoding these transport proteins.


METHODS
This review covers current research examining genetic polymorphisms in transporters expressed in the syncytiotrophoblast and evidence supporting the involvement of these transporters in the transport of oral antidiabetic agents. The aim is to provide insight into how the transfer of antidiabetic drugs across the placental trophoblast may be altered by polymorphisms in drug transporters.


CONCLUSIONS
There is a paucity of studies examining the influence of polymorphisms on transporter activity in the placenta and how the transfer of oral antidiabetics may be altered. Further research employing in vivo models is required to allow for the prediction of the potential consequences of polymorphisms on placental transporter expression and function.
Hospital for Sick Children, Motherisk Laboratory, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. erika.pollex@utoronto.ca
Erika K
EK
Pollex
Janine R
JR
Hutson
D000818:Animals; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000378:metabolism*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011247:Pregnancy
D007004:Hypoglycemic Agents; D026901:Membrane Transport Proteins