Effect of the XbaI polymorphism of estrogen receptor alpha on postmenopausal gray matter

• Published in: Neuroscience letters Vol. 434; no. 3; pp. 304 - 309
• Main Authors: Boccardi, Marina, Scassellati, Catia, Ghidoni, Roberta, Testa, Cristina, Benussi, Luisa, Bonetti, Matteo, Bocchio-Chiavetto, Luisella, Gennarelli, Massimo, Binetti, Giuliano, Frisoni, Giovanni B.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 04.04.2008
• Subjects: Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Atrophy - genetics; Atrophy - metabolism; Atrophy - physiopathology; Brain - metabolism; Brain - pathology; Brain - physiopathology; Cognition Disorders - genetics; Cognition Disorders - metabolism; Cognition Disorders - physiopathology; Cytoprotection - genetics; Dementia - genetics; Dementia - metabolism; Dementia - physiopathology; Deoxyribonucleases, Type II Site-Specific; Disease Progression; DNA Mutational Analysis; Estrogen receptor alpha; Estrogen Receptor alpha - genetics; Estrogens - metabolism; Female; Gene Frequency; Genetic Predisposition to Disease - genetics; Genetic Testing; Genotype; Heterozygote; Humans; Magnetic Resonance Imaging; Middle Aged; Morphometry; Neuroimaging; Polymorphism, Genetic - genetics; Polymorphism, Restriction Fragment Length; Postmenopause - metabolism; VBM; XbaI; Neuroimaging; VBM; Estrogen receptor alpha; XbaI; Morphometry; MR
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2008.01.076

The frequent polymorphism XbaI (A351G) in the estrogen receptor alpha (ERalpha) gene has been associated with some postmenopausal pathologies’ risk such as Alzheimer's disease (AD) or cognitive decline. In the present study, we explored whether the XbaI polymorphism leads to different gray matter volumes using voxel-based morphometry (VBM) on 20 magnetic resonance images of healthy postmenopausal women. Subjects carrying the less common XbaI/X allele were contrasted to non-carriers in groups well balanced by relevant confounding variables. The XbaI/X allele carriers displayed clusters ranging from 9 to 28% of tissue reductions in the cerebellar (cluster size, z, stereotactic coordinates: 16 mm 3; 3.17; 14, −94, −38) and cerebral cortex, in particular in the occipital lobe (272 mm 3; 3.76; −38,−68,−16), in the middle frontal gyrus (192 mm 3; 3.71; 38, 12, 38) and in the middle temporal gyrus, while the opposite comparison was negative. The XbaI/X allele in ERalpha gene is associated to smaller gray matter volumes of the cerebral and cerebellar cortex. This allele might increase the susceptibility for senile neurodegenerative conditions, being associated to smaller cerebral reserve.