Genetic Association Between KIBRA Polymorphism and Alzheimer's Disease with in a Japanese Population

KIBRA plays an important role in synaptic plasticity in human hippocampus related to cognitive function. Functional studies suggest that KIBRA is a potential candidate gene for memory and Alzheimer's disease (AD) risk. A single nucleotide polymorphism, Rs17070145 C allele affects the onset of AD in an age-dependent manner comparing with T/T genotypes and is also associated with risk of substance abuse and relapse. The aim of this case-control study was to investigate whether the rs17070145 polymorphism affected the onset of AD in an age-dependent manner in a Japanese population. We analysed KIBRA and APOE genotypes in 237 young AD cases, 154 age-matched control cases and 160 old AD cases. The analyses were performed by stratifying alcohol consumption and the APOE status. We used single photon emission computed tomography (SPECT) to analyse patients with AD with the rs17070145 polymorphism. The genotypic and allelic frequencies of the young AD group differed significantly from those of control and old AD groups. There was a significant association among high alcohol consumption (HAC-AD group) and the genotypic and allelic frequencies of the rs17070145 polymorphism. Logistic regression analyses demonstrate synergism between the APOE genotype and the rs17070145 C allele to increase the risk of AD in the young group; this was confirmed in the HAC-AD group. The SPECT study revealed hyperperfusion in the C allele carrier group was detected in the right inferior frontal gyrus compared with the T/T group. KIBRA rs17070145 affects specific phenotypes of patients with AD.