Sexually dimorphic effect of the Val66Met polymorphism of BDNF on susceptibility to Alzheimer's disease: New data and meta-analysis.
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.
Fukumoto
Noriko
N
Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Fujii
Takashi
T
Combarros
Onofre
O
Kamboh
M Ilyas
MI
Tsai
Shin-Jen
SJ
Matsushita
Sachio
S
Nacmias
Benedetta
B
Comings
David E
DE
Arboleda
Humberto
H
Ingelsson
Martin
M
Hyman
Bradley T
BT
Akatsu
Hiroyasu
H
Grupe
Andrew
A
Nishimura
Agnes Lumi
AL
Zatz
Mayana
M
Mattila
Kari M
KM
Rinne
Juha
J
Goto
Yu-ichi
Y
Asada
Takashi
T
Nakamura
Shun
S
Kunugi
Hiroshi
H
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*
D019208:Brain-Derived Neurotrophic Factor; D017931:DNA Primers; D008715:Methionine; D014633:Valine