Association of Apolipoprotein e with Intracerebral Hemorrhage Risk by Race/Ethnicity : A Meta-analysis
Marini, Sandro (Massachusetts General Hospital (Boston))
Crawford, Katherine (Massachusetts General Hospital (Boston))
Morotti, A. (Fondazione Mondino IRCCS, Pavia)
Lee, M. J. (Massachusetts General Hospital (Boston))
Pezzini, Alessandro (Università degli Studi di Brescia)
Moomaw, C. J. (University of Cincinnati)
Flaherty, M. L. (University of Cincinnati)
Montaner, Joan (Hospital Universitari Vall d'Hebron)
Roquer González, Jaume (Institut Hospital del Mar d'Investigacions Mèdiques)
Jimenez-Conde, Jordi (Institut Hospital del Mar d'Investigacions Mèdiques)
Giralt Steinhauer, Eva (Institut Hospital del Mar d'Investigacions Mèdiques)
Elosua, Roberto (Institut Hospital del Mar d'Investigacions Mèdiques)
Cuadrado-Godia, Elisa (Institut Hospital del Mar d'Investigacions Mèdiques)
Soriano Tarraga, Carolina (Institut Hospital del Mar d'Investigacions Mèdiques)
Slowik, A. (Jagiellonian University Medical College, Kraków)
Jagiella, Jeremiasz M (Jagiellonian University Medical College, Kraków)
Pera, J. (Jagiellonian University Medical College, Kraków)
Urbanik, Andrzej (Jagiellonian University Medical College, Kraków)
Pichler, A. (Jagiellonian University Medical College, Kraków)
Hansen, Björn M (Lund University)
McCauley, J. L. (John P. Hussman Institute for Human Genomics, Miami)
Tirschwell, D. L. (University of Washington)
Selim, Magdy (Beth Israel Deaconess Medical Center, Boston)
Brown, D. L. (University of Michigan)
Silliman, Scott L. (University of Florida College of Medicine)
Worrall, B. B. (University of Virginia Health System)
Meschia, J. F. (Mayo Clinic, Jacksonville, Florida)
Kidwell, C. S. (University of Arizona)
Testai, F. D. (University of Illinois)
Kittner, S. J. (University of Maryland School of Medicine)
Schmidt, H. (Medical University of Graz)
Enzinger, C. (Medical University of Graz)
Deary, Ian J. (University of Edinburgh)
Rannikmae, K. (University of Edinburgh)
Samarasekera, N. (University of Edinburgh)
Salman, R. A. S. (University of Edinburgh)
Sudlow, C. L. (University of Edinburgh)
Klijn, C. J. M. (UMC Utrecht Brain Center Rudolf Magnus)
Van Nieuwenhuizen, K. M. (UMC Utrecht Brain Center Rudolf Magnus)
Fernandez-Cadenas, Israel (Institut d'Investigació Biomèdica Sant Pau)
Delgado Martínez, María Pilar (Hospital Universitari Vall d'Hebron)
Norrving, B. (Lund University)
Lindgren, A. (Lund University)
Goldstein, J. N. (Massachusetts General Hospital (Boston))
Viswanathan, Anand (Massachusetts General Hospital (Boston))
Greenberg, S. M. (Massachusetts General Hospital (Boston))
Falcone, G. J. (Yale University)
Biffi, Alessandro (Massachusetts General Hospital (Boston))
Langefeld, Carl D (Wake Forest University, Winston-Salem, North Carolina)
Woo, D. (University of Cincinnati College of Medicine)
Rosand, J. (Massachusetts General Hospital (Boston))
Anderson, C. D. (Massachusetts General Hospital (Boston))
Universitat Autònoma de Barcelona

Data:	2019
Resum:	Importance: Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. Objective: To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) ϵ4 alleles, the most potent genetic risk factor for ICH. Design, Setting, and Participants: This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. Main Outcomes and Measures: Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. Results: In total, 13124 participants (7153 [54. 5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE ϵ2 (odds ratio [OR], 1. 49; 95% CI, 1. 24-1. 80; P <. 001) and APOE ϵ4 (OR, 1. 51; 95% CI, 1. 23-1. 85; P <. 001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE ϵ4 was associated with lobar ICH risk among Hispanic (OR, 1. 14; 95% CI, 1. 03-1. 28; P =. 01) but not in black (OR, 1. 02; 95% CI, 0. 98-1. 07; P =. 25) participants. APOE ϵ2 and ϵ4 did not show an association with nonlobar ICH risk in any race/ethnicity. Conclusions and Relevance: APOE ϵ4 and ϵ2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	African Americans ; Aged ; Aged, 80 and over ; Apolipoproteins E ; Case-Control Studies ; Cerebral Hemorrhage ; European Continental Ancestry Group ; Female ; Genetic Predisposition to Disease ; Hispanic Americans ; Humans ; Hypertension ; Male ; Middle Aged ; Risk Factors ; United States
Publicat a:	JAMA Neurology, Vol. 76 Núm. 4 (april 2019) , p. 480-491, ISSN 2168-6157

DOI: 10.1001/jamaneurol.2018.4519
PMID: 30726504

12 p, 544.9 KB

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