Uncoupling protein 2 polymorphisms as risk factors for NTDs.
BACKGROUND
Both environmental and genetic factors are involved in the etiology of NTDs. Inadequate folate intake and obesity are important environmental risk factors. Several folate-related genetic variants have been identified as risk factors; however, little is known about how genetic variants relate to the increased risk seen in obese women. Uncoupling Protein 2 (UCP2) is an attractive candidate to screen for NTD risk because of its possible role in obesity as well as energy metabolism, type-2 diabetes, and the regulation of reactive oxygen species. Interestingly, a previous study found that a common UCP2 compound homozygous genotype was associated with a threefold increase in NTD risk.


METHODS
We evaluated three polymorphisms, -866G>A, A55V, and the 3'UTR 45 bp insertion/deletion, as risk factors for NTDs in Irish NTD cases (n = 169), their mothers (n = 163), their fathers (n = 167), and normal control subjects (n = 332).


RESULTS
Allele and genotype frequencies were not significantly different when comparing NTD mothers, NTD fathers, or affected children to controls. Additionally, the previously reported risk genotype (combined homozygosity of 55VV and 3'UTR 45 bp deletion/deletion) was not present at a higher frequency in any NTD group when compared to controls.


CONCLUSIONS
In our Irish study population, UCP2 polymorphisms did not influence NTD risk. Moreover, the prevalence of this allele in other populations was similar to the Irish prevalence but far lower than reported in the previous NTD study, suggesting that this previous finding of an association with NTDs might have been due to an unrepresentative study sample.
Mitchell
Adam
A
Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Institute, 50 South Drive, Bethesda, MD 20892-8004, USA.
Pangilinan
Faith
F
Van der Meer
Julie
J
Molloy
Anne M
AM
Troendle
James
J
Conley
Mary
M
Kirke
Peadar N
PN
Scott
John M
JM
Brody
Lawrence C
LC
Mills
James L
JL
D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D007494:Ireland; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D009436:Neural Tube Defects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2