Search

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetic factors play an important role in the Alzheimer's disease (AD) development and memory impairment is a cardinal clinical feature of AD. Kidney and brain expressed protein (KIBRA), owing to its connection with human episodic memory, became an interesting candidate gene for AD. Recently, KIBRA (rs17070145) was reported to be associated with AD in the genetic and functional levels in Caucasian and African-American, and the association might be different across age groups. To investigate the possibility of age-dependent association of KIBRA with AD in Asian, we conducted an independent replication study in a cohort of 1,586 subjects from Han Chinese (including 790 LOAD patients and 796 healthy controls). The results revealed no significant differences in the distributions of genotype or allele between LOAD and control groups in the total sample. However, when these data were stratified by their age, we observed a significant difference in the genotypes and alleles frequencies (genotype: p = 0.004, allele: p = 0.035) in the young subgroup. Moreover, the association was further demonstrated in logistic regression analysis (rs17070145: p = 0.045, OR = 0.428). Our data suggested that KIBRA might associate with younger AD patients (≤74 years) in a Northern Han Chinese population.

Mitochondrial dysfunction is an early defect in the pathogenesis of late-onset Alzheimer's disease (LOAD). One interesting candidate gene for mitochondrial dysfunction in LOAD is the translocase of outer mitochondrial membrane 40 homolog (TOMM40) gene. Several single nucleotide polymorphisms (SNPs) within TOMM40 have been shown to affect susceptibility to LOAD in Caucasians, while there are no studies on the association of the polymorphisms with LOAD risk in Han Chinese. Here, the association of TOMM40 polymorphisms in LOAD was investigated in a large Northern Han Chinese cohort consisting of 1,578 individuals. Both allelic and genotypic associations of three SNPs (rs157580, rs2075650, and rs11556505) with LOAD risk were observed in the total sample as well as in the non- APOE ε4 carriers. For rs1160985, the allele and genotype frequencies differed significantly only in APOE ε4 carriers. After adjustment for age, gender, and APOE ε4 status, the association remained statistically significant only for the rs157580 but not for rs2075650 and rs11556505. In contrast, the rs1160985 exhibited significant risk effect after adjustment. In addition, haplotype analysis confirmed that the haplotypes derived from SNPs in rs2075650, rs11556505, and rs1160985 were associated with either risk or protective effects. In summary, our findings suggest that the TOMM40 polymorphisms may play a role in the pathogenesis of LOAD in Han Chinese.