Associationsof KIBRA Genepolymorphisms With Dementia:TheMIND-China Study

Background:Previous clinical studies have investigated the associations of KIBRA rs17070145 polymorphism with episodic memory and Alzheimer’s disease(AD)but the results are inconsistent.We aim to examine the associations of common KIBRA variants and haplotypes with dementia and its subtypes among rural-dwelling older adults.Methods:This population-based study included 5,466 participants(age≥60 years,57.3%women)in the baseline assessments of MIND-China study.In March-September 2018,data were collected through face-to-face interviews,clinical examinations,laboratory tests,and neuropsychological tests.KIBRA rs17070145 and coding region of KIBRA were sequenced using multiple-PCR amplification analysis.Dementia,AD,and vascular dementia(VaD)were diagnosed following the international criteria.Data were analyzed using multiple logistic regression models.Results:Dementia was diagnosed in 281 persons(182 with AD;88 with VaD),and 57.2%,36.7%,and 6.0%carried the KIBRA rs17070145 TT,CT,and CC genotypes,respectively.KIBRA rs17070145 CC genotype(vs.TT)displayed significant associations with multiadjusted odds ratio(OR)of 1.81(95%confidence interval 1.13-2.90)for dementia,1.38(0.712.68)for AD,and 2.17(1.07-4.36)for VaD,respectively.After adjusted for history of stroke,the association attenuate to 1.72(1.06-2.80)for dementia and became insignificant to 1.86(0.88-3.93)for VaD.Exonic SNPs rs3822660 and rs3822659 were in linkage disequilibrium(LD)with rs17070145(D’=0.88,R2=0.06).In addition,the CGT haplotype of these three SNPs was associated with dementia with a multi-adjusted OR of 1.29(1.05-1.58).Conclusion:The KIBRA rs17070145 and related haplotypes are associated with dementia,primarily driven by VaD,among rural-dwelling older adults.Stroke and the LD between rs17070145 and two exonic SNPs may partially explain the detrimental role of KIBRA rs17070145 C allele in dementia.