Friday 01 August, 2014

Gene May Help Identify Risk of Alzheimer’s in African Americans

Published On: Sun, Apr 14th, 2013 | Alzheimer's | By BioNews

Researchers at Mayo Clinic in Florida participated in a nationwide study that found minor differences between genes that contribute to late-onset Alzheimer’s disease in African-Americans and in Caucasians.

The study, published April 10 in The Journal of the American Medical Association, was the first to look at the genetics of a large number of African-Americans diagnosed with this common form of Alzheimer’s disease (1,968 patients) compared to 3,928 normal elderly African-American control participants.

The Alzheimer’s Disease Genetics Consortium conducted the study, which included Mayo Clinic in Florida investigators Neill R. Graff-Radford, M.D., and Nilufer Ertekin-Taner, M.D., Ph.D. They provided genetic samples and data from their Alzheimer’s disease databank.

Regional Association Plot of the ABCA7 Region (±100 Kilobases) in the African American Sample and the White Sample Described in Naj et al5 Based on the GRCh37/hg19 Genome Build (Image Credit: JAMA)

Regional Association Plot of the ABCA7 Region (±100 Kilobases) in the African American Sample and the White Sample Described in Naj et al5 Based on the GRCh37/hg19 Genome Build (Image Credit: JAMA)

The study found that the most common risk factor in these African-American patients was the APOE gene, which is also true for Caucasians with the disorder. In addition, another gene, ABCA7, which was discovered to be a risk locus for Caucasians, was also a significant risk factor in African-American patients.

The study concluded that association with variants at the ABCA7 gene increased the risk for late-onset Alzheimer’s disease approximately 1.8-fold in these African-American patients compared to 1.1-fold to 1.2-fold in individuals of European ancestry, although the biologic implications of this difference remains to be established.

Still, these differences may not fully explain the genetic basis for development of Alzheimer’s disease, the researchers say. The disorder is believed to arise from a number of different genes along with environmental influences.

“While they require replication in an independent African-American cohort, these findings imply that at least some of the genetic factors that lead to late-onset Alzheimer’s disease are shared between the two ethnic groups,” says Dr. Ertekin-Taner.

But the researchers also acknowledge that the seemingly greater influence of ABCA7 gene in African-Americans might contribute in some important, and as yet unknown, way to the disease, and it may have implications for developing targets for genetic testing, prevention, and treatment.

“These are early days in our understanding of Alzheimer’s disease in this group, and in others,” says Dr. Neill Graff-Radford. Dr. Ertekin-Taner adds: “It should be noted that these genetic association studies cannot identify the actual variant within the ABCA7 gene that causes the actual biologic change which ultimately confers risk for Alzheimer’s disease. Thus, further studies are needed to determine whether the same functional variants or different ones are operating in these two ethnic groups. This knowledge may be critical in drug and biomarker development efforts.”

“The importance of this study is that it is proof-of-principle study in this under-studied population and may pave the wave for future larger studies in African-Americans, as well as encourage similar studies in other non-Caucasian ethnic groups,” says Dr. Ertekin-Taner.

The study was supported by the National Institutes of Health (P50AG16574 and R01 AG032990).

Reference:
Reitz C, Jun G, Naj A, et al. Variants in the ATP-Binding Cassette Transporter (ABCA7), Apolipoprotein E ?4,and the Risk of Late-Onset Alzheimer Disease in African Americans. JAMA. 2013;309(14):1483-1492. doi:10.1001/jama.2013.2973.

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