Dataset Information

Association of SOD2, a mitochondrial antioxidant enzyme, with gray matter volume shrinkage in alcoholics.

ABSTRACT: Chronic alcoholism leads to gray matter shrinkage and induces the formation of superoxide anions (O(2)(-)) that can cause neuronal cell death. The mitochondrial superoxide dismutase 2 (SOD2) enzyme is critical in the metabolism of superoxide. An Ala16Val polymorphism putatively affects SOD2 enzyme activity in vivo. Brain volumes of 76 treatment-seeking alcohol-dependent individuals were measured with a 1.5T MRI. Intracranial tissue margins were manually outlined on coronal sections. Gray matter, white matter, sulcal, and ventricular CSF volumes were estimated using intensity-based K-means clustering. Ala16Val (rs4880) and a second haplotype tagging SNP, rs10370, were genotyped. The q-value package was used to correct for multiple comparisons. In the alcoholics, cerebrospinal fluid and intra-cranial volumes showed significant differences across the six diplotype categories. The homozygous Ala16-containing diplotype rs10370TT-rs4880GG was associated with lowest gray matter ratio (greater shrinkage; p=0.005). Presence of one or two copies of the low activity Ala16 allele was a risk factor for lower gray matter volume in alcoholics below the median alcohol consumption (p=0.03) but not in alcoholics above this level. White matter ratio was associated with sex (p=0.002) and lifetime total alcohol consumption (p=0.01) but not with diplotypes. In this exploratory analysis, a putative functional missense variant of SOD2 appears to influence gray matter loss in alcoholics. This may be due to impaired clearance of reactive oxygen species formed as a result of alcohol exposure. The risk/protective effect was observed in alcoholics with lower levels of lifetime alcohol consumption. Highest levels of exposure may overwhelm the protective action of the SOD2 enzyme.

SUBMITTER: Srivastava V

PROVIDER: S-EPMC3055396 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Association of SOD2, a mitochondrial antioxidant enzyme, with gray matter volume shrinkage in alcoholics.

Srivastava Vibhuti V Buzas Beata B Momenan Reza R Oroszi Gabor G Pulay Attila J AJ Enoch Mary-Anne MA Hommer Daniel W DW Goldman David D

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20091230 5

Chronic alcoholism leads to gray matter shrinkage and induces the formation of superoxide anions (O(2)(-)) that can cause neuronal cell death. The mitochondrial superoxide dismutase 2 (SOD2) enzyme is critical in the metabolism of superoxide. An Ala16Val polymorphism putatively affects SOD2 enzyme activity in vivo. Brain volumes of 76 treatment-seeking alcohol-dependent individuals were measured with a 1.5T MRI. Intracranial tissue margins were manually outlined on coronal sections. Gray matter, ...[more]

PMID: 20043000

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Dataset Information

Association of SOD2, a mitochondrial antioxidant enzyme, with gray matter volume shrinkage in alcoholics.

Publications

Association of SOD2, a mitochondrial antioxidant enzyme, with gray matter volume shrinkage in alcoholics.

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