The 894G>T variant in the endothelial nitric oxide synthase gene and spina bifida risk.
The 894G>T single nucleotide polymorphism (SNP) in the endothelial NOS (NOS3) gene, has recently been associated with embryonic spina bifida risk. In this study, a possible association between the NOS3 894G>T SNP and spina bifida risk in both mothers and children in a Dutch population was examined using both a case-control design and a transmission disequilibrium test (TDT). Possible interactions between the NOS3 894G>T SNP and the MTHFR 677C>T SNP, elevated plasma homocysteine, and decreased plasma folate concentrations were also studied. The NOS3 894TT genotype did not increase spina bifida risk in mothers or children (OR 1.50, 95%CI 0.71-3.19 and OR 1.78, 95%CI 0.75-4.25, respectively). The TDT demonstrated no preferential transmission of the NOS3 894T allele (Chi2=0.06, P=0.81). In combination with the MTHFR 677TT genotype or elevated plasma homocysteine concentrations, the NOS3 894GT/TT genotype increased maternal spina bifida risk (OR 4.52, 95%CI 1.55-13.22 and OR 3.38, 95%CI 1.46-7.84, respectively). In our study population, the NOS3 894GT/TT genotype might be a risk factor for having a spina bifida affected child in mothers who already have an impaired homocysteine metabolism.
van der Linden
Ivon J M
IJM
Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Heil
Sandra G
SG
Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
den Heijer
Martin
M
Department of Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.|Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Blom
Henk J
HJ
Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. h.blom@vumc.nl.|Metabolic Unit, PK 1-X-018, Department of Clinical Chemistry, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. h.blom@vumc.nl.
D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016135:Spinal Dysraphism / Q000209:etiology / Q000235:genetics*
D052250:Nitric Oxide Synthase Type III