Abstract
Background and aims: Substantial evidence supports the hypothesis that impairment of mitochondrial function and increased oxidative damage are involved in the pathogenesis of several neurodegenerative disorders including Alzheimer’s disease (AD). Manganese Superoxide dismutase (MnSOD) plays a major role in protecting the mitochondrion from oxidative damage due to Superoxide radicals and other excited oxygen species. Recent studies have indicated that MnSOD mRNA levels are significantly increased in the lymphocytes of AD patients, supporting the role of oxidative alterations in the pathogenetic mechanism underlying this neurodegeneration. A potentially functional amino acid polymorphism (Ala-9Val) has been described in the signal sequence of enzymes associated with decreased defense capacity against oxidative stress. The object of this study was to investigate the association between this polymorphism of the MnSOD gene and AD in the Italian population. Methods: The Ala-9Val polymorphism was genotyped by PCR amplification and SSCP analysis in 227 AD patients and 198 healthy controls. Results: No significant differences in genotype or allele frequencies between cases and controls, even after stratification for APOE carrier status, were observed. Conclusions: Our data suggest that the Ala-9Val polymorphism in the MnSOD gene is not associated with genetic susceptibility in AD patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Halliwell B. Reactive oxygen species and the central nervous system. J Neurochem 1992; 59: 1609–23.
Smith MA, Rottkamp CA, Nunomura A, Raina AK, Perry G. Oxidative stress in Alzheimer’s disease. Biochim Biophys Acta 2000; 1502: 139–44.
Venarucci D, Venarucci V, Vallese A, et al. Free radicals: important cause of pathologies refer to ageing. Panminerva Med 1999; 41: 335–9.
De Leo ME, Borrello S, Passantino M, et al. Oxidative stress and overexpression of manganese Superoxide dismutase in patients with Alzheimer’s disease. Neurosci Lett 1998; 250: 173–6.
Shimoda-Matsubayashi S, Matsumine H, Kobayashi T, Nakagawa-Hattori Y, Shimizu Y, Mizuno Y. Structural dimorphism in the mitochondrial targeting sequence in the human manganese super-oxide dismutase gene. A predictive evidence for conformational change to influence mitochondrial transport and a study of allelic association in Parkinson’s disease. Biochem Biophys Res Commun 1996; 226: 561–5.
Sutton A, Khoury H, Prip-Buus C, Cepanec C, Pessayre D, Degoul F. The Alal6Val genetic dimorphism modulates the import of human manganese Superoxide dismutase into rat liver mitochondria. Pharmacogenetics 2003; 13: 145–57.
Hu XF, Zhang XR, Xuan A, Cao XR. Association between Apolipoprotein E gene polymorphism and the patients with persistent vegetative state in the Chinese. Acta Genet Sin 2002; 29: 757–60.
Mitrunen K, Sillanpaa P, Kataja V, et al. Association between manganese Superoxide dismutase (MnSOD) gene polymorphism and breast cancer risk. Carcinogenesis 2001; 2: 827–9.
Van Landeghem GF, Tabatabaie P, Beckman G, Beckman L, Andersen PM. Manganese-containing Superoxide dismutase signal sequence polymorphism associated with sporadic motor neuron disease. Eur J Neurol 1999; 6: 639–44.
Kimura K, Isashiki Y, Sonoda S, Kakiuchi-Matsumoto T, Ohba N. Genetic association of manganese Superoxide dismutase with exudative age-related macular degeneration. Am J Ophthalmol 2000; 130: 769–73.
Hori H, Ohmori O, Shinkai T, et al. Manganese Superoxide dismutase gene polymorphism and schizophrenia: relation to tardive dyskinesia. Neuropsychopharmacology 2000; 23: 170–7.
Ryan KR, Jensen RE. Protein translocation across mitochondrial membranes: what a long, strange trip it is. Cell 1995; 83: 517–9.
Lemire BD, Fankhauser C, Baker A, Schatz G. The mitochondrial targeting function of randomly generated peptide sequences correlates with predicted helical amphiphilicity. J Biol Chem 1989; 264: 20206–15.
Shimoda-Matsubayashi S, Hattori T, Matsumine H, et al. Mn SOD activity and protein in a patient with chromosome 6-linked autosomal recessive parkinsonism in comparison with Parkinson’s disease and control. Neurology 1997; 49: 1257–62.
Checkoway H, Farin FM, Costa-Mallen P, Kirchner SC, Costa LG. Genetic polymorphisms in Parkinson’s disease. Neurotoxicology 1998; 19: 635–43.
Borgstahl GE, Parge HE, Hickey MJ, et al. Human mitochondrial manganese Superoxide dismutase polymorphic variant Ile58Thr reduces activity by destabilizing the tetrameric interface. Biochemistry 1996; 35: 4287–97.
Matsumine H, Saito M, Shimoda-Matsubayashi S, et al. Localization of a gene for an autosomal recessive form of juvenile Parkinsonism to chromosome 6q25.2-27. Am J Hum Genet 1997; 60: 588–96.
Semba RD, Blaum C, Guralnik JM, Moncrief DT, Ricks MO, Fried LP. Carotenoid and vitamin E status are associated with indicators of sarcopenia among older women living in the community. Aging Clin Exp Res 2003; 15: 482–7.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ventriglia, M., Chiavetto, L.B., Scassellati, C. et al. Lack of association between MnSOD gene polymorphism and sporadic Alzheimer’s Disease. Aging Clin Exp Res 17, 445–448 (2005). https://doi.org/10.1007/BF03327410
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03327410