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Home All Specialties Chronic Disease

New gene variants linked with Alzheimer Disease in African Americans

bys25qthea
April 9, 2013
in Chronic Disease, Neurology
Reading Time: 3 mins read
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Image: PD. PET scans of healthy vs. diseased brains

1. ABCA7 variants are associated with an increased risk of Alzheimer Disease in African Americans, more so than in non-Hispanic whites.

2. ABCA7 encodes an ATP binding cassette transporter, which interacts with apolipoproteins and thus affects lipid metabolism.

Study Rundown: In this retrospective meta-analysis, the researchers observed an association between a single-nucleotide polymorphism (SNP) in the ABCA7 region and risk of Alzheimer disease in African Americans. Not only did this finding reach genome-wide significance, but its effect size was relatively large as well. This study was unique because it specifically targeted African Americans, and it is the largest of its kind to study Alzheimer disease in this population.

The results are particularly noteworthy given a plausible mechianism, as ABCA7 is involved in lipid metabolism. This knowledge, in conjunction with the role of APOE genes, may help better elucidate the pathophysiology of this complex disease. In the future, targeted genetic screening may be used for disease risk assessments. In addition, the fact that some SNPs continue to be identified as associated with Alzheimer disease, regardless of the population being studied, contributes to the idea that they are important for disease susceptibility. The limitations of this study are few, but important given that Alzheimer is a complex disease with both heritable and environmental components. This study does not assess the contribution of other influences, such as multiple rare variants or structural variants, as it only identified susceptibility loci. As an inherent limitation, the identified loci may not be the ones causing disease, but rather may be in linkage disequilibrium with others that are and cannot be identified yet.

Click to read the study, published today in JAMA

Click to read an accompanying editorial in JAMA

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In-Depth [retrospective, case-control meta-analysis]: The study included a total of 5896 African Americans aged 60 or older, 1,968 of whom were case participants and 3,928 of whom were control participants. Genome wide analyses were conducted in order to identify associations between SNPs, which were either genotyped or imputed, and Alzheimer disease. Additionally, directed studies were conducted to look for similar associations with loci previously reported in the literature. A novel finding from this study is an association between Alzheimer disease and a SNP in ABCA7, which achieved genome-wide significance (odds ratio (OR) 1.79, p = 2.2 x 10-9). Furthermore, the effect size of the aforementioned gene is similar to that of the well known APOE OR 2.31, p = 5.5 x 10-47). Finally, four other susceptibility loci (CR1, BIN1, EPHA1, CD33), which were previously described in the literature for non-Hispanic whites, were shown again to be significantly associated with Alzheimer disease.

By Anne Marie Walters and Rif Rahman

© 2013 2minutemedicine.com. All rights reserved. No works may be reproduced without written consent from 2minutemedicine.com. Disclaimer: We present factual information directly from peer reviewed medical journals. No post should be construed as medical advice and is not intended as such by the authors or by 2minutemedicine.com. PLEASE SEE A HEALTHCARE PROVIDER IN YOUR AREA IF YOU SEEK MEDICAL ADVICE OF ANY SORT. Content is produced in accordance with fair use copyrights solely and strictly for the purpose of teaching, news and criticism. No benefit, monetary or otherwise, is realized by any participants or the owner of this domain.

 

Tags: ABCA7alzheimergeriatrics
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