Polymorphism in the manganese superoxide dismutase gene

Noha Elsayed Salama El Sakka, Nigel Robert Webster, Helen Frances Galley

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Oxidative stress and mitochondrial damage occur in sepsis. Manganese superoxide dismutase (MnSOD) provides the main defence against oxidative stress within mitochondria. Ala9Val is a single nucleotide polymorphism (SNP) in the MnSOD gene, predicted to affect intra- mitochondrial transport of the enzyme. We found a significant difference in the genotype frequency between healthy subjects (n = 100) and patients with sepsis (n = 40, p = 0.009). For assessment of functionality ten healthy subjects of each homozygous genotype (A/ A or V/ V) were studied. Peripheral blood mononuclear cells were separated and incubated for 18 h with lipopolysaccharide (LPS), followed by analysis of mitochondrial and cytosolic fractions. There was no difference between genotypes in MnSOD activity and cytochrome c concentration, and minor differences in total antioxidant capacity (TAC) and mitochondrial membrane potential, which did not affect response to LPS. Despite predictions from structural enzyme studies that mitochondrial trafficking would be affected by the Ala9Val polymorphism of the MnSOD gene had little functional effect.

Original languageEnglish
Pages (from-to)770-778
Number of pages9
JournalFree Radical Research
Volume41
Issue number7
DOIs
Publication statusPublished - Jan 2007

Keywords

  • manganese superoxide dismutase
  • antioxidants
  • oxidative stress
  • genetics
  • polymorphism
  • sepsis
  • mitochondrial targeting sequence
  • tumor-necrosis-factor
  • antioxidant capacity
  • Parkinsons-disease
  • lipid-peroxidation
  • organ dysfunction
  • endothelial-cells
  • sepsis syndrome
  • human monocytes

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