HOXA1 A218G polymorphism is associated with smaller cerebellar volume in healthy humans.

BACKGROUND AND PURPOSE The Homeobox A1 (HOXA1) gene plays a critical role during development of the hindbrain in mice. Little is currently known about the relation between this gene and human brain development. The HOXA1 A218G polymorphism has been found to be associated with autism and larger head circumference in autistic patients. Similar effects were revealed also in healthy children but not in adult controls. The aim of this study was to investigate the role of the A218G polymorphism on the hindbrain structure of healthy adults. METHODS Healthy persons from two independent groups underwent 3-dimensional high resolution magnetic resonance (MR) exam. Group A was made of 80 persons (27 G allele carriers and 53 non-carriers) and Group B of 72 (26 carriers and 46 non-carriers). Statistical parametric mapping 2 (SPM2) were used to perform voxel-based analysis of the gray matter (GM) of the hindbrain in carriers and non. Significance threshold was set at .05 with small volume correction using a cerebellar mask. RESULTS In Group A, G carriers exhibited decreased GM volume in the superior posterior and anterior lobe of the cerebellum bilaterally. In Group B, decreased GM volume were found across the entire left cerebellar cortex. CONCLUSIONS These data suggest that the HOXA1 A218G polymorphism may affect cerebellar development in humans. J Neuroimaging 2009;19:353-358.