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An exploratory study on CLU, CR1 and PICALM and Parkinson disease.

ABSTRACT: BACKGROUND:Recent GWAS and subsequent confirmation studies reported several single-nucleotide polymorphisms (SNPs) at the CLU, CR1 and PICALM loci in association with late-onset Alzheimer's disease (AD). Parkinson disease (PD) shares several clinical and pathologic characteristics with AD; we therefore explored whether these SNPs were also associated with PD risk. METHODOLOGY/PRINCIPAL FINDINGS:791 non-Hispanic Whites cases and 1,580 matched controls were included in the study. Odds ratios (OR) and 95% confidence intervals (CI) were obtained from logistic regression models. rs11136000 at the CLU locus was associated with PD risk under the recessive model (comparing TT versus CC+CT: OR?=?0.71, 95% CI: 0.55-0.92, p?=?0.008) after adjusting for year of birth, gender, smoking, and caffeine intake. Further adjustment for family history of PD and ApoE ?4 status did not change the result. In addition, we did not find evidence for effect modification by ApoE or known PD risk factors. The association, however, appeared to be stronger for PD with dementia (OR?=?0.49, 95% CI: 0.27-0.91) than for PD without dementia (OR?=?0.81, 95% CI: 0.61-1.06). The two other SNPs, rs6656401 from CR1, and rs3851179 from PICALM region were not associated with PD (p>0.05). CONCLUSION:Our exploratory analysis suggests an association of CLU with PD. This exploratory finding and the role of dementia in explaining this finding needs further investigation.

SUBMITTER: Gao J

PROVIDER: S-EPMC3166161 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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An exploratory study on CLU, CR1 and PICALM and Parkinson disease.

Gao Jianjun J Huang Xuemei X Park Yikyung Y Hollenbeck Albert A Chen Honglei H

PloS one 20110830 8

<h4>Background</h4>Recent GWAS and subsequent confirmation studies reported several single-nucleotide polymorphisms (SNPs) at the CLU, CR1 and PICALM loci in association with late-onset Alzheimer's disease (AD). Parkinson disease (PD) shares several clinical and pathologic characteristics with AD; we therefore explored whether these SNPs were also associated with PD risk.<h4>Methodology/principal findings</h4>791 non-Hispanic Whites cases and 1,580 matched controls were included in the study. Od ...[more]

PMID: 21912625

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Project description:BackgroundGenetic variants at the CLU, CR1, 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.MethodsWe pursued an association study between single nucleotide polymorphism genotypes at the CLU, CR1, 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), CR1 (rs6656401, rs3818361), and PICALM (rs3851179) were genotyped 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 ε4 dosage.ResultsWe identified nominally significant or suggestive associations between the LOAD-risky CR1 variants and worse Logical Memory immediate recall scores in blacks (P = .068-.046, β = -2.7 to -1.2). The LOAD-protective CLU variant is associated with better logical memory endophenotypes in white subjects (P = .099-.027, β = 0.31-0.93). The CR1 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.ConclusionThese results suggest for the first time that LOAD risk variants at CR1 may influence memory endophenotypes in blacks. In addition, the CLU LOAD-protective variant may confer enhanced memory in whites. Although these results would not remain significant after stringent corrections for multiple testing, they need to be considered in the context of the LOAD associations with which they have biological consistency. They also provide estimates for effect sizes on memory endophenotypes that could guide future studies. The detection of memory effects for these variants in clinically normal subjects, implies that these LOAD risk loci might modify memory prior to clinical diagnosis of AD.

Dataset Information

An exploratory study on CLU, CR1 and PICALM and Parkinson disease.

Publications

An exploratory study on CLU, CR1 and PICALM and Parkinson disease.

Similar Datasets

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