Increased risk for Alzheimer disease and younger age of onset seen with APOE<\/em> \u03b53 R145C missense variation<\/p>\n<\/h3>\n By Elana Gotkine HealthDay Reporter<\/b><\/p>\n <\/b><\/p>\n WEDNESDAY, Feb. 22, 2023 (HealthDay News) — For individuals of African ancestry, the APOE<\/em> \u00ce\u00b53 R145C missense variant is associated with an increased risk for Alzheimer disease (AD), according to a study published in the Feb. 21 issue of the Journal of the American Medical Association<\/em>.<\/p>\n Yann Le Guen, Ph.D., from Stanford University in California, and colleagues examined whether amino acid changes to APOE<\/em> specific to individuals of African ancestry modulate the risk for AD. The study combined a case-control study using a sequenced discovery sample (stage 1; 2,888 cases and 4,957 controls) followed by two microarray imputed datasets (stage 2, internal replication [1,201 cases and 2,744 controls] and stage 3, external validation [733 cases and 19,406 controls]). Two APOE<\/em> missense variants were assessed (R145C and R150H). Individuals included in the study were of African ancestry.<\/p>\n The researchers found that R145C was present in 4.8 and 1.5 percent of participants with AD and controls in stage 1 and was associated with an increased risk for AD (odds ratio, 3.01; 95 percent confidence interval, 1.87 to 4.85) and reported younger age at AD onset (\u00ce\u00b2, \u00e2\u0088\u00925.87 years). In stage 2, the association with increased AD risk was replicated; R145C was present in 4.7 and 2.7 percent of those with AD and controls (odds ratio, 2.20; 95 percent confidence interval, 1.04 to 4.65), with concordant results observed in stage 3 (R145C present in 3.8 and 2.7 percent, respectively; odds ratio, 1.90; 95 percent confidence interval, 0.99 to 3.64). In stages 2 and 3, the association with earlier AD onset was also replicated (\u00ce\u00b2, \u00e2\u0088\u00925.23 and \u00e2\u0088\u009210.15 years, respectively).<\/p>\n “With additional external validation, the findings may inform AD genetic risk assessment in individuals of African ancestry,” the authors write.<\/p>\n Abstract\/Full Text (subscription or payment may be required)<\/a><\/p>\n <\/i><\/p>\n