Risk factors for neural tube defects: associations between uncoupling protein 2 polymorphisms and spina bifida.
BACKGROUND
Polymorphisms in the mitochondrial membrane transporter gene UCP2 are capable of affecting energy metabolism, body weight regulation, and possibly preventing the buildup of reactive oxygen species, all factors that could contribute to neural tube defect risk through maternal obesity and diabetes.


METHODS
Genomic DNA was extracted from newborn screening blood spots obtained from infants with spina bifida and nonmalformed control infants. Genotype frequencies of two genetic variants in the UCP2 gene, an amino acid substitution of valine for alanine at codon 55 in exon 4, and a 45-base pair insertion/deletion in the 3' untranslated region of exon 8,were determined by restriction enzyme digestion of PCR amplification products.


RESULTS
We found the frequency of the 3' untranslated region deletion homozygous genotype (256/256) as well as the A55V homozygous (Val/Val) genotype to be higher in SB infants than in controls (odds ratio [OR], 3.1; 95% confidence interval [CI], 0.9-10.4 and OR = 2.0; 95% CI = 0.3-11.1, respectively). Additionally, the frequency of the combined homozygous 256/256,+ / + genotype was higher in cases and resulted in more than a threefold higher spina bifida risk (OR = 3.6; 95% CI = 1.0-13.1).


CONCLUSIONS
These data are the first to suggest that polymorphisms in the UCP2 gene may be genetic risk factors of spina bifida.
Volcik
Kelly A
KA
Institute of Bioscience and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030-3303, USA.
Shaw
Gary M
GM
Zhu
Huiping
H
Lammer
Edward J
EJ
Finnell
Richard H
RH
D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D004247:DNA / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D016017:Odds Ratio; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011506:Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D016135:Spinal Dysraphism / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D004247:DNA