Lack of association between the leptin receptor gene (LEPR) Gln223Arg polymorphism and late-onset Alzheimer disease.
The principal hypothesis for pathogenesis of Alzheimer disease (AD) is the amyloid cascade hypothesis, which emphasizes an imbalance between production and clearance of beta-amyloid (Abeta) in the brain. Insulin has important effects on the regulation of the Abeta level in the brain, modulating both Abeta production and clearance. An optimal brain insulin level promotes Abeta clearance, which may play protective roles against AD. A functional human leptin receptor gene (LEPR) polymorphism, a glutamine to an arginine substitution at codon 223 (Gln223Arg), has been associated with insulin resistance capacity and an altered leptin-binding activity. The LEPR Gln223Arg polymorphism may thus play an important role in the pathogenesis of AD. In this study, we examined the association between the LEPR Gln223Arg polymorphism and late-onset Alzheimer disease (LOAD) in a Japanese population. Our sample includes 49 patients with LOAD and 134 normal controls. Our preliminary data showed no significant association between the LEPR Gln223Arg polymorphism and LOAD (genotype distribution: chi=0.11, df=2, P=0.945; allele frequency: chi=0.058, df=1, P=0.81, odds ratio=1.08, 95% confidence interval=0.59 to 2.03). Our results suggest that the LEPR polymorphism may not play a major role in the development of LOAD.
Utsunomiya
Kensuke
K
Department of Psychiatry, University of Occupational and Environmental Health, Yahatanishi-ku Kitakyushu, Japan. k-utsu@med.uoeh-u.ac.jp
Shinkai
Takahiro
T
Sakata
Shinichi
S
Hwang
Rudi
R
Yamada
Kenji
K
Chen
Hsin-I
HI
Fukunaka
Yuko
Y
Ohmori
Osamu
O
Nakamura
Jun
J
D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D054411:Receptors, Leptin / Q000235:genetics*
C515448:LEPR protein, human; D054411:Receptors, Leptin