RT Journal Article
SR Electronic
T1 Genetic Correlations of Brain Lesion Distribution in Multiple Sclerosis: An Exploratory Study
JF American Journal of Neuroradiology
JO Am. J. Neuroradiol.
FD American Society of Neuroradiology
DO 10.3174/ajnr.A2352
A1 M.H. Sombekke
A1 M.M. Vellinga
A1 B.M.J. Uitdehaag
A1 F. Barkhof
A1 C.H. Polman
A1 D. Arteta
A1 D. Tejedor
A1 A. Martinez
A1 J.B.A. Crusius
A1 A.S. Peña
A1 J.J.G. Geurts
A1 H. Vrenken
YR 2011
UL http://www.ajnr.org/content/early/2011/03/24/ajnr.A2352.abstract
AB BACKGROUND AND PURPOSE: In MS, the total brain lesion volume and spatial distribution of lesions across the brain vary widely among individual patients. We hypothesized that spatial distribution may be partially driven by genetic predisposition, and we aimed to explore relations among candidate genes and the spatial distribution of white matter brain lesions in MS. MATERIAL AND METHODS: Genotypes of 69 SNPs in 208 patients with MS were related to the spatial distribution of T2 brain lesions. Lesions were manually outlined on MR images, and binary lesion masks were produced and registered to a common space. With Randomise software, the lesion masks were related to genotype by using a voxelwise nonparametric GLM approach, followed by clusterwise analysis. We used a DNA chip with SNPs selected from the literature on MS susceptibility, severity, and phenotypes. RESULTS: For 11 of these SNPs, 1 of the genotypes expressed significant clusters of increased or decreased lesion probability in varying, predominantly periventricular, brain regions. When we statistically controlled the voxelwise analyses for effects of total brain lesion volume, only 1 SNP remained significant: rs2227139, located within the MHC class II region. This SNP retained its periventricular cluster of significantly increased lesion probability for the heterozygote genotype. CONCLUSIONS: Heterozygosity of rs2227139 (MHC class II region) is associated with increased right frontal periventricular lesion probability (P < .01). Ten other SNPs showed associations between genotype and spatial lesion distribution that are partly explained by total lesion volume.