title: Sexually dimorphic effect of the Val66Met polymorphism of BDNF on susceptibility to Alzheimer's disease: New data and meta-analysis.
abstract: Conflicting results have been reported as to whether genetic variations (Val66Met and C270T) of the brain-derived neurotrophic factor gene (BDNF) confer susceptibility to Alzheimer's disease (AD). We genotyped these polymorphisms in a Japanese sample of 657 patients with AD and 525 controls, and obtained weak evidence of association for Val66Met (P = 0.063), but not for C270T. After stratification by sex, we found a significant allelic association between Val66Met and AD in women (P = 0.017), but not in men. To confirm these observations, we collected genotyping data for each sex from 16 research centers worldwide (4,711 patients and 4,537 controls in total). The meta-analysis revealed that there was a clear sex difference in the allelic association; the Met66 allele confers susceptibility to AD in women (odds ratio = 1.14, 95% CI 1.05-1.24, P = 0.002), but not in men. Our results provide evidence that the Met66 allele of BDNF has a sexually dimorphic effect on susceptibility to AD.
authors.affiliation: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Fukumoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujii
authors.forename: Onofre
authors.initials: O
authors.lastname: Combarros
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
authors.forename: Shin-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.forename: Sachio
authors.initials: S
authors.lastname: Matsushita
authors.forename: Benedetta
authors.initials: B
authors.lastname: Nacmias
authors.forename: David E
authors.initials: DE
authors.lastname: Comings
authors.forename: Humberto
authors.initials: H
authors.lastname: Arboleda
authors.forename: Martin
authors.initials: M
authors.lastname: Ingelsson
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Hyman
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.forename: Andrew
authors.initials: A
authors.lastname: Grupe
authors.forename: Agnes Lumi
authors.initials: AL
authors.lastname: Nishimura
authors.forename: Mayana
authors.initials: M
authors.lastname: Zatz
authors.forename: Kari M
authors.initials: KM
authors.lastname: Mattila
authors.forename: Juha
authors.initials: J
authors.lastname: Rinne
authors.forename: Yu-ichi
authors.initials: Y
authors.lastname: Goto
authors.forename: Takashi
authors.initials: T
authors.lastname: Asada
authors.forename: Shun
authors.initials: S
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics*; D012727:Sex Characteristics; D014633:Valine / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D008715:Methionine; D014633:Valine