Several previous studies on the relationship between the insulin-degrading enzyme (IDE) gene and Alzheimer's disease (AD) have connected certain genetic variants to late-onset AD, in the absence of the apolipoprotein E (APOE)ε4 allele. However, the conclusions of these studies remain controversial. We investigated the association between two polymorphisms of IDE with AD in the Chinese population and found that the T/A genotype of rs4646958 had an important role in AD (adjusted p=0.007, odds ratio [OR]=2.796, 95% confidence interval [CI]=1.330-5.878), under the co-dominant genetic model. The T/C genotype of rs1887922 was also significantly associated with AD compared to the T/T genotype (adjusted p=0.003, OR=2.644, 95% CI=1.407-4.970). The C allele of rs1887922 conferred a higher risk of AD under the dominant genetics model (adjusted p=0.001, OR=2.719, 95% CI=1.472-5.022). Compared with the two other variant genotypes, the T/T genotype showed a protective effect in both polymorphisms (adjusted p=0.007, OR=0. 358, 95% CI=0.170-0.752 for rs4646958; adjusted p=0.001, OR=0. 368, 95% CI=0.199-0.679 in rs1887922). In the context of APOEε4-negative status, both variants were significantly associated with AD in some genetic models.
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