BACKGROUND: Clusterin (also called apolipoprotein J) has a potential central role in the pathogenesis of Alzheimer's disease (AD). Recently, two genome-wide association studies have identified three variants in CLU gene encoding clusterin associated with AD risk in Caucasians, while there are no studies on the association of CLU with AD risk in Asians. METHODS: The study investigated 324 sporadic late-onset AD (LOAD) and 388 healthy controls matched for sex and age in a Han Chinese population. Three common genetic variants (rs2279590, rs11136000 and rs9331888) in CLU gene were genotyped using MALDI-TOF mass spectrometry. RESULTS: The minor allele (G) of the rs9331888 polymorphism within CLU was significantly associated with an increased risk of LOAD (OR=1.39, 95% CI=1.13-1.72, P=0.002). Logistic regression analysis revealed that the rs9331888 polymorphism presented strong associations with LOAD in the dominant, recessive and additive models. No significant differences in genotype and allele frequencies of the rs2279590 and rs11136000 polymorphisms were found between LOAD patients and controls. Haplotype analysis identified a risk haplotype (CCG) (OR=1.66) and a protective haplotype (CCC)(OR=0.70). CONCLUSIONS: Our findings implicate CLU as a susceptibility gene for LOAD in Han Chinese. Copyright 2010 Elsevier B.V. All rights reserved.
BACKGROUND:Clusterin (also called apolipoprotein J) has a potential central role in the pathogenesis of Alzheimer's disease (AD). Recently, two genome-wide association studies have identified three variants in CLU gene encoding clusterin associated with AD risk in Caucasians, while there are no studies on the association of CLU with AD risk in Asians. METHODS: The study investigated 324 sporadic late-onset AD (LOAD) and 388 healthy controls matched for sex and age in a Han Chinese population. Three common genetic variants (rs2279590, rs11136000 and rs9331888) in CLU gene were genotyped using MALDI-TOF mass spectrometry. RESULTS: The minor allele (G) of the rs9331888 polymorphism within CLU was significantly associated with an increased risk of LOAD (OR=1.39, 95% CI=1.13-1.72, P=0.002). Logistic regression analysis revealed that the rs9331888 polymorphism presented strong associations with LOAD in the dominant, recessive and additive models. No significant differences in genotype and allele frequencies of the rs2279590 and rs11136000 polymorphisms were found between LOAD patients and controls. Haplotype analysis identified a risk haplotype (CCG) (OR=1.66) and a protective haplotype (CCC)(OR=0.70). CONCLUSIONS: Our findings implicate CLU as a susceptibility gene for LOAD in Han Chinese. Copyright 2010 Elsevier B.V. All rights reserved.