Effect of Bcl-2 rs956572 SNP on regional gray matter volumes and cognitive function in elderly males without dementia

Age (Dordr). 2013 Apr;35(2):343-52. doi: 10.1007/s11357-011-9367-5. Epub 2011 Dec 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Analysis of Variance
  • Chi-Square Distribution
  • Cognition Disorders / genetics*
  • Cognition Disorders / pathology*
  • Genes, bcl-2 / genetics*
  • Genotype
  • Homozygote
  • Humans
  • Image Interpretation, Computer-Assisted
  • Language Disorders / genetics
  • Language Disorders / pathology
  • Magnetic Resonance Imaging
  • Male
  • Neuropsychological Tests
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Sensitivity and Specificity
  • Taiwan
  • Temporal Lobe / pathology*