Complement receptor 1 polymorphisms and risk of late-onset Alzheimer's disease.

The amyloid beta-protein (Abeta)-induced complement system activation plays an important role in Alzheimer's disease (AD). Complement receptor 1 (CR1) is thought to contribute to Abeta clearance. A recent large genome-wide association study (GWAS) has identified significant association of two single nucleotide polymorphisms (SNPs) (rs6656401 and rs3818361) in the CR1 gene with AD in Caucasians. Here, we performed a case-control study to clarify whether the risk for sporadic late-onset AD (LOAD) might be influenced by these polymorphisms in a large Chinese cohort consisting of 254 patients and 357 healthy controls. The results revealed that there were significant differences in genotype (P=0.02) and allele (P=0.007) frequencies of the SNP rs6656401 but no in rs3818361 between AD patients and controls. The A allele of rs6656401 was associated with an increased risk of LOAD (P=0.007, odds ratios/OR =1.652). In the subgroup of APOE epsilon4 non-carriers, both the A of rs6656401 and T allele of rs3818361 were observed to be significantly higher in case than in controls (P=0.002 and P=0.035, respectively). For rs6656401, the logistic regression analysis revealed that the (AA +AG) genotypes has a 2.4-fold increased risk compared with the GG genotype (P=0.049). Haplotype analysis identified the AT haplotype to increase the risk of LOAD (P=0.03, OR=2.44). This study provides the evidence that variations in the CR1 gene play an important role in the pathogenesis of sporadic LOAD in the Han Chinese population. Copyright 2010 Elsevier B.V. All rights reserved.