Evidence that the risk of spina bifida is influenced by genetic variation at the NOS3 locus

Brown, Karen; Cook, Michelle; Hoess, Katy; Whitehead, Alexander S.; Mitchell, Laura E.

doi:10.1002/bdra.20002

Cited by 24 publications

(19 citation statements)

References 27 publications

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“…Potential joint effects of cigarette smoke on NOS3 genotype is of interest because of the demonstrated reduction of NOS3 transcription by cigarette smoking [Brown et al, 2004] and nitric oxide's involvement in cervical ripening [Chwalisz and Garfield, 1998;Tornblom et al, 2005]. No modification of preterm delivery risk by smoking was observed for any of the NOS3 polymorphisms in this study, as reported by Hao et al [2004].…”

Section: Discussionsupporting

confidence: 43%

Association between 49 infant gene polymorphisms and preterm delivery

Chen

Carmichael

Shaw

et al. 2007

American J of Med Genetics Pt A

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The occurrence of preterm delivery has been increasing in the U.S. Previous studies have identified risk factors for preterm delivery that may have genetic influences. We conducted a case-control study comparing the frequencies of 49 genetic polymorphisms among 62 preterm infants and 553 term infants. The polymorphisms that we examined were involved in xenobiotic-metabolism, blood pressure, coagulation, the inflammatory response, cell-cell interaction, or folate-homocysteine metabolism. Univariate analyses on the individual polymorphisms revealed a statistically significant effect for the variant genotypes compared to the wildtype genotypes in SERPINE1 11053G > T (OR = 0.4, 95% CI = 0.2-0.8). This finding suggests the coagulation/thrombophilic pathway may influence the development of preterm delivery.

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Section: Discussionsupporting

confidence: 43%

Association between 49 infant gene polymorphisms and preterm delivery

Chen

Carmichael

Shaw

et al. 2007

American J of Med Genetics Pt A

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“…to possessing null alleles of NOS3 [Brown et al, 2004]. The results shown in Table IV reveal some evidence for higher risk of conotruncal defects in infants whose mothers smoked cigarettes periconceptionally and who had one of the variant alleles (dominant model) for NOS3 A(À922)G or NOS3 glu298asp compared to those infants whose mothers did not smoke and whose genotypes were wild-type.…”

Section: Resultsmentioning

confidence: 79%

Risks of human conotruncal heart defects associated with 32 single nucleotide polymorphisms of selected cardiovascular disease-related genes

Shaw

Iovannisci²,

Yang

et al. 2005

Am. J. Med. Genet.

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Investigating possible genetic polymorphisms and gene-environment interactions in the etiology of human conotruncal defects is a prudent research approach. In this study we explore gene-only and gene-environment effects of 32 single nucleotide polymorphisms (SNPs) on conotruncal defect risks. The genes bearing these SNPs participate in one of five pathogenetic processes, homocysteine metabolism, coagulation, cell-cell interaction, inflammatory response, and blood pressure regulation. We used DNA samples and data from a California population-based case-control interview study (1987-1988 birth cohort). We employed a multilocus allele-specific hybridization assay. Allelic variants were determined by genotyping 155 infants with conotruncal defects (cases) and 437 infants without malformations (controls). Among the 32 SNPs, four were associated with odds ratios of 2 or more, and two with odds ratios of 0.5 or less. The four SNPs were F2 G20210A (prothrombin) with an odds ratio of 2.5 (95% confidence interval; 0.9-7.0), F7 promoter (-323) 10-bp del/ins with an odds ratio of 2.3 (0.8-6.8), ITGB3 leu33pro (platelet glycoprotein IIIa) with an odds ratio of 2.2 (0.9-5.7), and NPPA T2238C (atrial natriuretic precursor peptide) with an odds ratio of 2.9 (0.8-10.1). Two SNPs were associated with decreased risks: TNF (tumor necrosis factor, G (-376A)) and ADD1 gly460trp (alpha adducin) with odds ratios of 0.5 (0.1-2.3) and 0.5 (0.2-1.9), respectively. Analyses that investigated a potential gene-nutrient interaction between maternal periconceptional vitamin use and MTHFR genotypes did not indicate that the CT or TT genotype contributed to conotruncal defect risk in infants even in the absence of maternal use of multivitamin supplements with folic acid. Analyses that investigated a potential interaction on risk between NOS3 genes and maternal cigarette smoking, revealed some evidence for higher risk of conotruncal defects in infants whose mothers smoked cigarettes periconceptionally and who had one of the variant alleles for NOS3 A(-922G) or NOS3 glu298asp compared to those infants whose mothers did not smoke and whose genotypes were wild-type. Our results provide some support for involvement of genetic variation of biologically relevant candidate genes for some birth defects whose pathogenesis may be related to altered vascular tone or integrity. In particular, NPPA appears to be a good candidate gene for conotruncal defects and warrants further investigation.

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“…Likewise, the LRT comparing the full model (model 1) with the model omitting the parameters that index the maternal genotype was not statistically significant ( 2 2 ϭ 1.53, p ϭ 0.46). Similar conclusions, regarding maternal genotypic effects for ABCC2 C(-24)T, were obtained when trios composed of the proband's mother and maternal grandparents (mother trios) were analyzed using the TDT and a likelihood ratio test (as described in (Doolin et al 2002;Brown et al, 2004)) using both complete and incomplete mother trios (data not shown). …”

Section: Resultsmentioning

confidence: 58%

“…The study data were obtained from a previously described, ongoing investigation of the genetics of spina bifida in which families that include at least one affected (i.e., with meningocele, meningomyelocele, or myelocele) member are ascertained through several sources (Doolin et al, 2002;Brown et al, 2004). The present study is based on data from 353 families that were ascertained between November 1997 and July 2003 from the Spina Bifida Clinic and the Center for Fetal Diagnosis and Therapy, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; the Spinal Dysfunction Clinic at the Alfred I. duPont Hospital for Children, Wilmington, Delaware; advertisements in professional and support group newsletters; and other sources.…”

Section: Study Subjectsmentioning

confidence: 99%