DNMBP is genetically associated with Alzheimer dementia in the Belgian population

• Published in: Neurobiology of aging 2009-12, Vol.30 (12), p.2000-2009
• Main Authors: Bettens, Karolien, Brouwers, Nathalie, Engelborghs, Sebastiaan, De Pooter, Tim, De Deyn, Peter P, Sleegers, Kristel, Van Broeckhoven, Christine
• Format: Article
• Language: English
• Subjects: Aged; Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Alzheimer's disease; Apolipoprotein E4 - genetics; Association study; Belgium - epidemiology; Biological and medical sciences; Chromosome 10; Cytoskeletal Proteins - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Development. Senescence. Regeneration. Transplantation; Dynamin binding protein gene; Female; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Haplotypes; Humans; Internal Medicine; Linkage Disequilibrium; Male; Medical sciences; Middle Aged; Neurology; Polymorphism, Single Nucleotide; Sequence Analysis, DNA; Vertebrates: nervous system and sense organs
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2008.02.003

Abstract Genetic association of the dynamin binding protein gene ( DNMBP ) on chromosome 10 with late-onset Alzheimer's disease (AD) was reported among Japanese. Here, we assessed the genetic role of DNMBP in an extended Belgian AD group using a gene-wide association approach. A total of 18 SNPs across the DNMBP locus were genotyped in 555 late-onset AD patients and 638 healthy control individuals. Significant associations were observed for two SNPs (rs3740057 and rs10883421). Haplotype analysis identified association with haplotype blocks in the 3’ region of DNMBP comprising rs2862919, rs11190302, rs10509739, rs2256700 and comprising rs3740057 and rs6584331. Stratification for APOE ε 4 status showed that association was only present in the APOE ε 4 negative subgroup. Sliding-window analyses provided further evidence for association with the 3’–end of DNMBP both for the total and for the APOE ε 4 negative group. Taken together our findings underscore a role for DNMBP in the genetic risk for late-onset AD in the Belgian population.