A common ABCC2 promoter polymorphism is not a determinant of the risk of spina bifida.
BACKGROUND
There is compelling evidence that the risk of spina bifida, a malformation of the caudal neural tube, is associated with maternal and/or embryonic disturbances in folate/homocysteine metabolism. Hence, functional variants of genes that influence folate/homocysteine metabolism constitute a biologically plausible group of candidate risk factors for spina bifida and other neural tube defects. One such candidate is ABCC2, the gene encoding ABCC2, (a.k.a. canalicular multispecific organic anion transporter [cMOAT], multidrug resistance related protein 2 [MRP2]), a member of the ABC transporter family that effluxes natural folates and anti-folate drugs such as methotrexate.


METHODS
The association between the risk of spina bifida and both the maternal and embryonic ABCC2 C(-24)T genotype was evaluated by using the transmission disequilibrium test and log-linear modeling.


RESULTS
These analyses provided no evidence that the risk of spina bifida was significantly related to either the maternal or embryonic ABCC2 C(-24)T genotype.


CONCLUSIONS
The results of the present analyses suggest that the C(-24)T variant of the ABCC2 gene is not a major determinant of spina bifida risk.
Jensen
Liselotte E
LE
Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Wall
Amelia M
AM
Cook
Michelle
M
Hoess
Katy
K
Thorn
Caroline F
CF
Whitehead
Alexander S
AS
Mitchell
Laura E
LE
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D005492:Folic Acid / Q000378:metabolism; D014644:Genetic Variation; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D016013:Likelihood Functions; D016014:Linear Models; D000089762:Multidrug Resistance-Associated Protein 2; D009436:Neural Tube Defects / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D016135:Spinal Dysraphism / Q000235:genetics*
C000715087:ABCC2 protein, human; D018528:ATP-Binding Cassette Transporters; D000089762:Multidrug Resistance-Associated Protein 2; D006710:Homocysteine; D005492:Folic Acid