title: Missense variants in CR1 are associated with increased risk of Alzheimer' disease in Han Chinese.
abstract: 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 ε4-carrying status, significance was observed in APOE ε4 non-carriers for rs116806486 and in APOE ε4 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 ε4 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.
authors.affiliation: Department of Neurology, Guiyang Hospital of Guizhou Aviation Industry Group, Guizhou, China; Department of Neurology, Affiliated Guizhou Aviation Industry Group 300 Hospital of Zunyi Medical University, Guizhou, China; Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Ma
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Sun
authors.forename: Dan
authors.initials: D
authors.lastname: Miao
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017463:Receptors, Complement 3b / Q000235:genetics*; D012306:Risk; D017422:Sequence Analysis, DNA
chemical_list: D001057:Apolipoproteins E; C509991:CR1 protein, human; D017463:Receptors, Complement 3b
keywords: Alzheimer's disease; Association; Complement receptor 1; Missense variants; Polymorphism