期刊
ALZHEIMERS & DEMENTIA
卷 10, 期 2, 页码 205-213出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2013.01.016
关键词
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资金
- National Institutes of Health grants
- National Institute on Aging [R01 AG032990, RO1 AG018023]
- Mayo Alzheimer's Disease Research Center [P50 AG016574]
- Mayo Alzheimer's Disease Patient Registry [U01 AG006786, K01 AG028573]
- National Institutes of Health [KL2 RR024151]
- Siragusa Foundation grants
- Disease Research Program
- Palumbo Professorship in Alzheimer's Disease Research
- GHR Foundation grant
Background: Genetic variants at the CLU, CRI, and PICALM loci associate with risk for late-onset Alzheimer's disease (LOAD) in genomewide association studies. In this study, our aim was to determine whether the LOAD risk variants at these three loci influence memory endophenotypes in black and white subjects. Methods: We pursued an association study between single nucleotide polymorphism genotypes at the CLU, CRI, and PICALM loci and memory endophenotypes. We assessed black subjects (AA series: 44 with LOAD and 224 control subjects) recruited at Mayo Clinic Florida and whites recruited at Mayo Clinic Minnesota (RS series: 372, with LOAD and 1690 control subjects) and Florida (JS series: 60 with LOAD and 529 control subjects). Single nucleotide polymorphisms at the LOAD risk loci CLU (rs11136000), CRI (rs6656401, rs3818361), and PICALM (rs3851179) were geno-tyed and tested for association with Logical Memory immediate recall, Logical Memory delayed recall, Logical Memory percent retention, Visual Reproduction immediate recall, Visual Reproduction delayed recall, and Visual Reproduction percent retention scores from the Wechsler Memory Scale Revised using multivariable linear regression analysis, adjusting for age at exam, sex, education, and apolipoprotein E 84 dosage. Results: We identified nominally significant or suggestive associdtions between the LOAD-risky CR1 variants and worse Logical Memory immediate recall scores in blacks (P =.068-0.46,beta = -2.7 to -1.2). The LOAD-protective CLU variant is associated with better logical memory endophenotypes in white subjects (P =.099-0.27, beta = 0.31-0.93). The CRI associations persisted when the control subjects from the AA series were assessed separately. The CLU associations appeared to be driven by one of the white series (RS) and were also observed when the control subset from RS was analyzed.
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