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.
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 ADpatients, 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 ADpatients 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 ADpatients.
Authors: David Gamarra; Xabier Elcoroaristizabal; Manuel Fernández-Martínez; Marian M de Pancorbo Journal: Dis Markers Date: 2015-12-01 Impact factor: 3.434