期刊
NEUROBIOLOGY OF AGING
卷 35, 期 2, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2013.08.009
关键词
Alzheimer's disease; Complement receptor 1; Polymorphism; Missense variants; Association
资金
- National Natural Science Foundation of China [81000544, 81171209]
- Shandong Provincial Natural Science Foundation, China [ZR2010HQ004, ZR2011HZ001]
- Shandong Provincial Outstanding Medical Academic Professional Program
Complement receptor 1 (CR1) has been considered to play an important role in late-onset Alzheimer's disease (LOAD) pathogenesis. To explore the correlation between the CR1 gene and LOAD, a 2-step design study was conducted in our Northern Han Chinese population. We first sequenced the promoter, exons, the 5' and 3' untranslated regions and exon-intron boundaries of CR1 in a small sample (n = 100). This allowed us to identify a total of 22 variants. In addition, 6 missense variants within the CR1 gene were selected to be genotyped in a total of 2292 individuals. Only 2 SNPs (rs116806486, Thr -> Ala; rs6691117, Ile/Val) were significantly associated with an increased risk of LOAD. After stratification by APOE epsilon 4-carrying status, significance was observed in APOE epsilon 4 non-carriers for rs116806486 and in APOE epsilon 4 carriers for rs6691117. Logistic analysis revealed that the rs116806486 polymorphism remained associated with LOAD in a dominant model, whereas the rs6691117 polymorphism was associated with LOAD in additive and recessive models but not in a dominant model after adjusting for sex, age at onset, and APOE epsilon 4 status. Examination of the haplotypes identified the risk of a 3-SNP (rs2274567, rs3737002, and rs6691117) haplotype ATG in CR1 was associated with an increased risk for LOAD. These findings provide the evidence that missense variants in the CR1 gene may be involved in LOAD pathologic process in Han Chinese. (C) 2014 Elsevier Inc. All rights reserved.
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