Lack of association between the leptin receptor gene (LEPR) Gln223Arg polymorphism and late-onset Alzheimer disease.

Abstract

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.

• Authors: Kensuke Utsunomiya, Takahiro Shinkai, Shinichi Sakata, Rudi Hwang, Kenji Yamada, Hsin-I Chen, Yuko Fukunaka, Osamu Ohmori, Jun Nakamura
• Journal: Alzheimer disease and associated disorders (Alzheimer Dis Assoc Disord) 2010 Jan-Mar Vol. 24 Issue 1 Pg. 101-3 ISSN: 1546-4156 [Electronic] United States
• PMID: 20220325 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• LEPR protein, human
• Receptors, Leptin

Topics

• Age of Onset
• Aged
• Aged, 80 and over
• Alzheimer Disease (genetics)
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Male
• Polymerase Chain Reaction
• Polymorphism, Single Nucleotide
• Receptors, Leptin (genetics)