Genetic variation in Clusterin gene and Alzheimer's disease risk in Han Chinese

Abstract: Clusterin gene (CLU), also known as apolipoprotein J (ApoJ), is a strong candidate gene for late-onset Alzheimer''s disease (LOAD) according to the Alzgene database. To further characterize this association and to isolate the variants contributing to the pathogenesis of LOAD in Han Chinese, we first sequenced a small sample (n = 100) to discover variants in the promoter, exons, the 5′ and 3′ untranslated regions, and exon–intron boundaries of CLU. Follow-up genotyping of identified variants in a larger sample (n = 1592). Sequencing analysis identified 18 variants. Analysis in the larger population revealed that only the rs9331949 C allele was significantly associated with an increased risk of LOAD, even after adjusting for multiple testing (p = 0.026). Logistic analysis identified the rs9331949 polymorphism was still strongly associated with LOAD (additive model: p = 0.004, odds ratio = 1.274; dominant model: p = 0.039, odds ratio = 1.239; recessive model: p = 0.002, OR = 1.975) after adjusting for sex, age, and APOE ε4 status. Our findings implicate CLU as a susceptibility gene for LOAD in Han Chinese. [Copyright &y& Elsevier]