APOE polymorphisms influence longitudinal lipid trends preceding intracerebral hemorrhage
Authors
Chia-Ling Phuah, Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Hemorrhagic Stroke Research Group (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Division of Behavioral Neurology (A.B.), Division of Psychiatry (A.B.), Department of Psychiatry, Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA.Follow
Miriam R. Raffeld, Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Hemorrhagic Stroke Research Group (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Division of Behavioral Neurology (A.B.), Division of Psychiatry (A.B.), Department of Psychiatry, Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA.
Alison M. Ayres, Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Hemorrhagic Stroke Research Group (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Division of Behavioral Neurology (A.B.), Division of Psychiatry (A.B.), Department of Psychiatry, Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA.
M Edip Gurol, Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Hemorrhagic Stroke Research Group (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Division of Behavioral Neurology (A.B.), Division of Psychiatry (A.B.), Department of Psychiatry, Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA.
Anand Viswanathan, Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Hemorrhagic Stroke Research Group (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Division of Behavioral Neurology (A.B.), Division of Psychiatry (A.B.), Department of Psychiatry, Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA.
Steven M. Greenberg, Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Hemorrhagic Stroke Research Group (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Division of Behavioral Neurology (A.B.), Division of Psychiatry (A.B.), Department of Psychiatry, Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA.
Alessandro Biffi, Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Hemorrhagic Stroke Research Group (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Division of Behavioral Neurology (A.B.), Division of Psychiatry (A.B.), Department of Psychiatry, Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA.
Jonathan Rosand, Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Hemorrhagic Stroke Research Group (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Division of Behavioral Neurology (A.B.), Division of Psychiatry (A.B.), Department of Psychiatry, Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA.
Christopher D. Anderson, Division of Neurocritical Care and Emergency Neurology (C.-L.P., J.R., C.D.A.), Center for Human Genetic Research (C.-L.P., M.R.R., A.B., J.R., C.D.A.), The J. Philip Kistler Stroke Research Center (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Hemorrhagic Stroke Research Group (A.M.A., M.E.G., A.V., S.M.G., J.R., C.D.A.), Division of Behavioral Neurology (A.B.), Division of Psychiatry (A.B.), Department of Psychiatry, Massachusetts General Hospital, Boston; and Program in Medical and Population Genetics (C.-L.P., A.B., J.R., C.D.A.), Broad Institute, Cambridge, MA.
Abstract
OBJECTIVE: We sought to determine whether APOE genotype influences a previously observed decline in serum total cholesterol (TC) and low-density lipoprotein (LDL) levels preceding primary intracerebral hemorrhage (ICH), as a potential demonstration of nonamyloid mechanisms of APOE in ICH risk. METHODS: We performed a single-center retrospective longitudinal analysis using patients with known APOE genotype drawn from an ongoing cohort study of ICH. Serum lipid measurements for TC, triglycerides (TGs), LDL, and high-density lipoprotein (HDL) collected within 2 years before and after index ICH were extracted from electronic medical records. Piecewise linear mixed-effects models were used to compare APOE allele-specific effects on temporal serum lipid trends in ICH. Demographics, medical history, medications, and health maintenance data were included as fixed effects. Inter- and intraindividual variations in lipid levels were modeled as random effects. RESULTS: A total of 124 ICH cases were analyzed. APOE ε4 carriers had greater rates of decline in serum TC and LDL within 6 months preceding ICH (TC: -7.30 mg/dL/mo, p = 0.0035; LDL: -8.44 mg/dL/mo, p = 0.0001). Conversely, serum TC and LDL levels in APOE ε2 carriers were unchanged within the same time period. APOE genotype had no associations with serum HDL or TG trends. CONCLUSIONS: APOE allele status predicts serum TC and LDL changes preceding acute ICH. Our results have implications for ongoing efforts in dissecting the role of dyslipidemia in cerebrovascular disease risk. APOE genotype-specific influence on lipid trends provides a clue for one mechanism by which APOE may influence risk of ICH. Further characterization of the metabolic roles of APOE is needed to improve the understanding of APOE biology in cerebrovascular disease risk.
Publication Date
8-1-2016
Publication Title
Neurology. Genetics
Digital Object Identifier (DOI)
10.1212/NXG.0000000000000081
Recommended Citation
Phuah, Chia-Ling; Raffeld, Miriam R.; Ayres, Alison M.; Gurol, M Edip; Viswanathan, Anand; Greenberg, Steven M.; Biffi, Alessandro; Rosand, Jonathan; and Anderson, Christopher D., "APOE polymorphisms influence longitudinal lipid trends preceding intracerebral hemorrhage" (2016). Neurology. 1711.
https://scholar.barrowneuro.org/neurology/1711
