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

The amyloid beta-protein (Aβ)-induced complement system activation plays an important role in Alzheimer's disease (AD). Complement receptor 1 (CR1) is thought to contribute to Aβ 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 ε4 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.