Linked Life Data

15887293

Source:http://linkedlifedata.com/resource/pubmed/id/15887293

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-5-26
pubmed:abstractText
Repairing DNA damage is critical during embryogenesis because development involves sensitive periods of cell proliferation, and abnormal cell growth or death can result in malformations. Knockout mouse experiments have demonstrated that disruption of DNA repair genes results in embryolethality and structural defects. Studies using mid-organogenesis rat embryos showed that DNA repair genes were variably expressed. It is hypothesized that polymorphisms that alter the functionality of DNA repair enzymes may modify the risk of malformations. We conducted a case-control analysis to investigate the relationship between DNA repair gene polymorphisms and the risk of spina bifida and oral clefts. Newborn screening blood spot DNA was obtained for 250 cases (125 spina bifida, 125 oral clefts) identified by the California Birth Defects Monitoring Program, and 350 non-malformation controls identified from birth records. Six single nucleotide polymorphisms of five DNA repair genes representing three distinct repair pathways were interrogated including: XRCC1 (Arg399Gln), APE1 (Asp148Glu), XRCC3 (Thr241Met), hOGG1(Ser326Cys), XPD (Asp312Asn, Lys751Gln). Elevated or decreased odds ratios (OR, adjusted for race/ethnicity) for spina bifida were found for genotypes containing at least one copy of the variant allele for XPD [751Gln, OR = 1.62; 95% confidence interval (CI) = 1.05-2.50] and APE 148 (OR = 0.58; CI = 0.37-0.90). A decreased risk of oral clefts was found for XRCC3 (OR = 0.62; CI = 0.39-0.99) and hOGG1 (326 Cys/Cys, OR = 0.22; CI = 0.06-0.78). This study suggested that polymorphisms of DNA repair genes, representing different major repair pathways, may affect risk of two major birth defects. Future, larger studies, examining additional repair genes, birth defects, and interaction with exposures are recommended.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1552-4825
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
135
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
268-73
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:15887293-Alleles, pubmed-meshheading:15887293-Case-Control Studies, pubmed-meshheading:15887293-Cleft Lip, pubmed-meshheading:15887293-Cleft Palate, pubmed-meshheading:15887293-DNA Glycosylases, pubmed-meshheading:15887293-DNA Helicases, pubmed-meshheading:15887293-DNA Repair, pubmed-meshheading:15887293-DNA-(Apurinic or Apyrimidinic Site) Lyase, pubmed-meshheading:15887293-DNA-Binding Proteins, pubmed-meshheading:15887293-Gene Frequency, pubmed-meshheading:15887293-Genetic Testing, pubmed-meshheading:15887293-Genotype, pubmed-meshheading:15887293-Humans, pubmed-meshheading:15887293-Infant, Newborn, pubmed-meshheading:15887293-Linkage Disequilibrium, pubmed-meshheading:15887293-Mouth Abnormalities, pubmed-meshheading:15887293-Mutation, Missense, pubmed-meshheading:15887293-Neonatal Screening, pubmed-meshheading:15887293-Odds Ratio, pubmed-meshheading:15887293-Polymorphism, Genetic, pubmed-meshheading:15887293-Risk Factors, pubmed-meshheading:15887293-Spinal Dysraphism, pubmed-meshheading:15887293-Transcription Factors, pubmed-meshheading:15887293-Xeroderma Pigmentosum Group D Protein
pubmed:year
2005
pubmed:articleTitle
Polymorphisms in DNA repair genes as risk factors for spina bifida and orofacial clefts.
pubmed:affiliation
Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA. andy_olshan@unc.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural