Dataset Information

ABCA7 and risk of dementia and vascular disease in the Danish population.

ABSTRACT: ATP-binding-cassette transporter A7(ABCA7) is suggested to be involved in lipid transport as well as in phagocytosis of amyloid-? in the brain. We tested the hypothesis that a common genetic variant in ABCA7 is associated with dementia, ischemic heart disease, ischemic cerebrovascular disease, and with lipid levels in the general population, independent of the common apolipoprotein E(APOE) genotype.For this purpose, we genotyped a common genetic variant in ABCA7, identified in genome-wide-association-studies of Alzheimer's disease, in 104,258 individuals from the Danish general population, and also meta-analyzed our results with publicly available consortia data.Multifactorially adjusted hazard ratios for Alzheimer's disease were 1.07 (95% confidence interval:0.93-1.23) and 1.72 (1.24-2.40) for GA and AA versus GG genotype. Results were similar after APOE genotype adjustment and when only APOE ?33 carriers were studied. Including 178,304 individuals, the meta-analyzed odds ratio for Alzheimer's disease per one allele ABCA7 rs4147929 increase was 1.15 (1.12-1.18). ABCA7 genotype was not convincingly associated with vascular dementia, ischemic heart disease, ischemic cerebrovascular disease, or with lipid levels. Including 288,563 individuals, meta-analyzed odds ratios for ischemic heart disease per one allele ABCA7 rs4147929 increase was 1.01 (0.99-1.03).A common genetic variant in ABCA7 was associated with high risk of Alzheimer's disease independent of APOE genotype. The lack of association with vascular dementia, ischemic heart disease, ischemic cerebrovascular disease, and with lipid levels suggests that ABCA7 is not important for atherosclerosis. Thus, our findings support the suggested role of ABCA7 in Alzheimer's disease pathology and phagocytic clearance of amyloid-? in the brain.

SUBMITTER: Kjeldsen EW

PROVIDER: S-EPMC5771325 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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<i>ABCA7</i> and risk of dementia and vascular disease in the Danish population.

Kjeldsen Emilie W EW Tybjærg-Hansen Anne A Nordestgaard Børge G BG Frikke-Schmidt Ruth R

Annals of clinical and translational neurology 20171219 1

<h4>Objective</h4>ATP-binding-cassette transporter A7(<i>ABCA7</i>) is suggested to be involved in lipid transport as well as in phagocytosis of amyloid-<i>β</i> in the brain. We tested the hypothesis that a common genetic variant in <i>ABCA7</i> is associated with dementia, ischemic heart disease, ischemic cerebrovascular disease, and with lipid levels in the general population, independent of the common apolipoprotein E(<i>APOE</i>) genotype.<h4>Methods</h4>For this purpose, we genotyped a com ...[more]

PMID: 29376091

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Project description:ObjectivesThe association between gout and dementia, Alzheimer's disease (AD), or vascular dementia (VD) is not fully understood. The aim of this meta-analysis was to evaluate the risk of all-cause dementia, AD, and VD in gout patients with or without medication.MethodsData sources were PubMed, Embase, the Cochrane Library, and reference lists of included studies. This meta-analysis included cohort studies assessing whether the risk of all-cause dementia, AD, and VD was associated with gout. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to access the overall certainty of evidence. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a random-effects model, and publication bias was assessed with funnel plots and Egger's test.ResultsA total of six cohort studies involving 2,349,605 individuals were included in this meta-analysis, which were published between 2015 and 2022. The pooling analysis shows that the risk of all-cause dementia was decreased in gout patients [RR = 0.67, 95% CI (0.51, 0.89), I2 = 99%, P = 0.005, very low quality], especially in gout patients with medication [RR = 0.50, 95% CI (0.31, 0.79), I2 = 93%, P = 0.003, low quality]. The risk of AD [RR = 0.70, 95% CI (0.63, 0.79), I2 = 57.2%, P = 0.000, very low quality] and VD [RR = 0.68, 95% CI (0.49, 0.95), I2 = 91.2%, P = 0.025, very low quality] was also decreased in gout patients. Despite the large heterogeneity, the sensitivity analysis indicated that the results were robust, and there was little evidence of publication bias.ConclusionThe risk of all-cause dementia, AD, and VD is decreased in gout patients, but the quality of evidence is generally low. More studies are still needed to validate and explore the mechanisms of this association.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022353312.

Dataset Information

ABCA7 and risk of dementia and vascular disease in the Danish population.

Publications

<i>ABCA7</i> and risk of dementia and vascular disease in the Danish population.

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