Uncoupling protein 2 polymorphisms as risk factors for NTDs |
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Authors: | Adam Mitchell Faith Pangilinan Julie Van der Meer Anne M. Molloy James Troendle Mary Conley Peadar N. Kirke John M. Scott Lawrence C. Brody James L. Mills |
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Affiliation: | 1. Molecular Pathogenesis Section, Genome Technology Branch, National Human Genome Research Institute, Building 50, Room 5306, 50 South Drive, MSC 8004, Bethesda, Maryland 20892‐8004;2. Department of Clinical Medicine, Trinity College Dublin, Dublin, Ireland;3. Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, Department of Health and Human Services, National Institutes of Health, Bethesda, Maryland 20892;4. Child Health Epidemiology Unit, Health Research Board, Dublin, Ireland;5. Department of Biochemistry, Trinity College Dublin, Dublin, Ireland |
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Abstract: | 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. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc. |
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Keywords: | neural tube defects spina bifida UCP2 obesity |
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