A study of the low-frequency CLU gene variant affecting the susceptibility to late-onset Alzheimer's disease and mild cognitive impairment / 中华老年医学杂志

ABSTRACT

Objective To explore the potential genetic variants related with late-onset Alzheimer's disease(LOAD),and to broaden the AD genetic susceptibility factor profile.Methods We targetedly sequenced four lipids metabolism related genes including apolipoprotein E(APOE),sortilin-related receptor gene (SORL 1),apolipoprotein C-I (APOC1) and clusterin (CLU),validated these candidate variants in patients with LOAD and mild cognitive impairment (MCI)and the controls with normal cognitive function,and made a bioinformatic analysis.Results The mutation in the allele of CLU rs117389184,a low-frequency single nucleotide polymorphism,would increase the risk of LOAD and MCI[OR (95 ％ CI)3.56 (1.08-4.84),P =0.026;OR (95 ％ CI)3.06 (0.98-4.03),P =0.026],suggesting CLU rs117389184 gene variant was associated with cognitive impairment.This variation could affect CLU gene expression by interfering with the binding of transcription factors.Conclusions CLU rs117389184 is a new genetic risk variant for LOAD and MCI.