Dataset Information

Novel single nucleotide polymorphisms in the superoxide dismutase 1 and 2 genes among children with myelomeningocele.

ABSTRACT:

Objective

Excessive oxidative stress has been demonstrated as a mechanism for neural tube defects (NTDs). The current exploratory study sought to examine sequence variations in the superoxide dismutase 1 (SOD1) and 2 (SOD2) genes in patients with myelomeningocele and to identify variants altering risk for myelomeningocele.

Study design

We sequenced deoxyribonucleic acid from 96 patients with myelomeningocele. The 11 exons were amplified by polymerase chain reaction, and the products were sequenced with the Sanger method. Results were compared with reference sequences (NM_000454, NM_000636, and NM_001024466) obtained from University of California Santa Cruz Genome Browser. Observed alleles that differed from the reference sequences were considered novel variants.

Results

We found 1 novel variant and 1 variant only recently described in phase 1 of the 1000 Genomes Project but not yet validated. The novel variant is located in the 3'-untranslated region (UTR) of SOD2 and is present in 2 of 96 patients (1.0% allele frequency). The other variant is located in the 3'-UTR of SOD1 and is present in 2 of 96 patients (1.0% allele frequency). Minor allele frequencies of known single nucleotide polymorphisms were compared with unaffected population controls.

Conclusion

We identified 1 novel variant and made the second report of an additional variant in the SOD genes studied. The variant located in the 3'-UTR of SOD1 is predicted to alter microribonucleic acid (miRNA) binding. The variant located in the 3'-UTR of SOD2 is predicted to alter 2 miRNA binding sites and potentially affects messenger ribonucleic acid production. We also identified 2 known single-nucleotide polymorphisms that occur in significantly different frequency compared with the unaffected population controls.

SUBMITTER: Kase BA

PROVIDER: S-EPMC3786042 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

Novel single nucleotide polymorphisms in the superoxide dismutase 1 and 2 genes among children with myelomeningocele.

Kase Benjamin A BA Northrup Hope H Au Kit Sing KS

American journal of obstetrics and gynecology 20130620 4

<h4>Objective</h4>Excessive oxidative stress has been demonstrated as a mechanism for neural tube defects (NTDs). The current exploratory study sought to examine sequence variations in the superoxide dismutase 1 (SOD1) and 2 (SOD2) genes in patients with myelomeningocele and to identify variants altering risk for myelomeningocele.<h4>Study design</h4>We sequenced deoxyribonucleic acid from 96 patients with myelomeningocele. The 11 exons were amplified by polymerase chain reaction, and the produc ...[more]

PMID: 23792044

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Project description:Selenium may affect prostate cancer risk via its plasma carrier selenoprotein P which shows dramatically reduced expression in prostate cancer tumors and cell lines. The selenoprotein P (SEPP1) Ala234 single nucleotide polymorphism (SNP) allele is associated with lower plasma selenoprotein P in men, reducing the concentration/activity of other antioxidant selenoproteins. Selenium status also modifies the effect of the mitochondrial superoxide dismutase (SOD2) SNP Ala16Val on prostate cancer risk. We investigated the relationship of these SNPs with prostate cancer risk. DNA from 2,975 cases and 1,896 age-matched controls from the population-based Prostate Cancer in Sweden study were genotyped using TaqMan assays. Cases were designated aggressive or nonaggressive prostate cancers at diagnosis by clinical criteria. Association with prostate cancer was investigated by logistic regression; gene-gene interaction using a general linear model. The mean plasma selenium concentration measured in 169 controls was relatively low (76.0 +/- 17.2 microg/L). SNP genotype distributions were in Hardy-Weinberg equilibrium. SOD2-Ala16+ men were at a greater risk of prostate cancer [odds ratios (OR), 1.19; 95% confidence intervals (CI), 1.03-1.37] compared with SOD2-Val16 homozygotes. Men homozygous for SEPP1-Ala234 who were also SOD2-Ala16+ had a higher risk of prostate cancer (OR, 1.43; 95% CI, 1.17-1.76) and aggressive prostate cancer (OR, 1.60; 95% CI, 1.22-2.09) than those who were SOD2-Val16 homozygotes (interaction, prostate cancer P = 0.05; aggressive prostate cancer P = 0.01). This interaction was stronger in ever-smokers: SOD2-Ala16+ men homozygous for SEPP1-Ala234 had an almost doubled risk of prostate cancer (OR, 1.97; 95% CI, 1.33-2.91; interaction P = 0.001). In a low-selenium population, SOD2-Ala16+ men homozygous for SEPP1-Ala234 are at an increased risk of prostate cancer/aggressive prostate cancer especially if ever-smokers, because they are likely to produce more mitochondrial H(2)O(2) that they cannot remove, thereby promoting prostate tumor cell proliferation and migration.

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Dataset Information

Novel single nucleotide polymorphisms in the superoxide dismutase 1 and 2 genes among children with myelomeningocele.

Objective

Study design

Results

Conclusion

Publications

Novel single nucleotide polymorphisms in the superoxide dismutase 1 and 2 genes among children with myelomeningocele.

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