Effect of Bcl-2 rs956572 SNP on regional gray matter volumes and cognitive function in elderly males without dementia
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The Bcl-2 gene is a major regulator of neural plasticity and cellular resilience. A single-nucleotide polymorphism (SNP) in the Bcl-2 gene, Bcl-2 rs956572, significantly modulates the expression of Bcl-2 protein and cellular vulnerability to apoptosis. This study investigated the association between the Bcl-2 rs956572 SNP and brain structural abnormalities in non-demented elders, and to test the relationship between neuropsychological performance and regional gray matter (GM) volumes. Our sample comprised 97 non-demented elderly men with a mean age of 80.6 ± 5.6 years (range, 65 to 92 years). Cognitive test results, magnetic resonance imaging, and genotyping of Bcl-2 rs956572 were examined for each subject. The differences in regional GM volumes between G homozygotes and A-allele carriers were tested using optimized voxel-based morphometry. Subjects with G homozygotes exhibited significantly worse performance in the language domain of the Cognitive Abilities Screening Instrument (CASI; p = 0.009). They also showed significantly smaller GM volumes in the right middle temporal gyrus (MTG) (BA 21), but larger GM volumes in the left precuneus (BA 31), right lingual gyrus (BA 18), and left superior occipital gyrus (BA 19) relative to A-allele carriers (p < 0.001). A trend toward a positive correlation between right MTG GM volumes and the language domain of CASI was also evident (r = 0.181; p = 0.081). The findings suggest that Bcl-2 rs956572 SNP may modulate cognitive function and regional GM volume in non-demented elderly men, and that this polymorphism may affect language performance through its effect on the right MTG.
KeywordsBcl-2 MRI Volumetry Cognition Aged Polymorphism
This work was supported in part by Taipei Veterans General Hospital (V98ER3-004, VGHUST100-G7-1-2), National Science Council (NSC 97-2314-B-075-001-MY3, NSC 98-2923-B-010-001-MY3 and NSC 100-2628-E-010-002-MY3) and Cheng Hsin Hospital – Yang-Ming University (99F167CY02). The authors also acknowledge MR support from the MRI Core Laboratory of National Yang-Ming University that was funded from the Ministry of Education of Taiwan (Aim for the Top University Plan).
- Caraci F, Chisari M, Frasca G, Canonico PL, Battaglia A, Calafiore M, Battaglia G, Bosco P, Nicoletti F, Copani A, Sortino MA (2005) Nicergoline, a drug used for age-dependent cognitive impairment, protects cultured neurons against beta-amyloid toxicity. Brain Res 1047:30–37PubMedCrossRefGoogle Scholar
- Krug A, Markov V, Krach S, Jansen A, Zerres K, Eggermann T, Stöcker T, Shah NJ, Nöthen MM, Georgi A, Strohmaier J, Rietschel M, Kircher T (2011) Genetic variation in G72 correlates with brain activation in the right middle temporal gyrus in a verbal fluency task in healthy individuals. Hum Brain Mapp 32:118–126PubMedCrossRefGoogle Scholar
- Machado-Vieira R, Pivovarova NB, Stanika RI, Yuan P, Wang Y, Zhou R, Zarate CA Jr, Drevets WC, Brantner CA, Baum A, Laje G, McMahon FJ, Chen G, Du J, Manji HK, Andrews SB (2011) The Bcl-2 gene polymorphism rs956572AA increases inositol 1,4,5-trisphosphate receptor-mediated endoplasmic reticulum calcium release in subjects with bipolar disorder. Biol Psychiatry 69:344–352PubMedCrossRefGoogle Scholar
- Martinou JC, Dubois-Dauphin M, Staple JK, Rodriguez I, Frankowski H, Missotten M, Albertini P, Talabot D, Catsicas S, Pietra C, Huarte J (1994) Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13:1017–1030PubMedCrossRefGoogle Scholar
- Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59(Suppl 20):22–33PubMedGoogle Scholar
- Smith CD (2011) Structural imaging in early pre-states of dementia. Biochim Biophys Acta. doi: 10.1016/j.bbadis.2011.07.002
- Sultana R, Banks WA, Butterfield DA (2010) Decreased levels of PSD95 and two associated proteins and increased levels of BCl2 and caspase 3 in hippocampus from subjects with amnestic mild cognitive impairment: insights into their potential roles for loss of synapses and memory, accumulation of Abeta, and neurodegeneration in a prodromal stage of Alzheimer's disease. J Neurosci Res 88:469–477PubMedGoogle Scholar
- Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain: 3-dimensional proportional system—an approach to cerebral imaging. Thieme Medical Publishers, New YorkGoogle Scholar