Burden of risk alleles for hypertension increases risk of intracerebral hemorrhage.[Erratum appears in Stroke. 2012 Nov;43(11):e171]

MedStar author(s):
Citation: Stroke. 43(11):2877-83, 2012 Nov.PMID: 22933587Institution: MedStar Heart & Vascular InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Multicenter Study | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov'tSubject headings: *Genetic Predisposition to Disease/ge [Genetics] | *Hypertension/ge [Genetics] | *Intracranial Hemorrhage, Hypertensive/ge [Genetics] | Aged | Alleles | Case-Control Studies | Female | Genotype | Humans | Hypertension/co [Complications] | Male | Polymorphism, Single Nucleotide | Risk FactorsLocal holdings: Available online from MWHC library: 1970 - present, Available in print through MWHC library: 1999 - 2006ISSN:
  • 0039-2499
Name of journal: Stroke; a journal of cerebral circulationAbstract: BACKGROUND AND PURPOSE: Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN.CONCLUSIONS: Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.METHODS: We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables.RESULTS: No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score.All authors: Ayres AM, Biffi A, Broderick JP, Brown DL, Cuadrado-Godia E, Delgado P, Devan WJ, Elosua R, Enzinger C, Falcone GJ, Fernandez-Cadenas I, Flaherty ML, Giralt-Steinhauer E, Goldstein JN, Greenberg SM, Hansen BM, International Stroke Genetics Consortium, Jagiella JM, Jimenez-Conde J, Kidwell CS, Kissela B, Kleindorfer DO, Langefeld CD, Lindgren A, Meschia JF, Montaner J, Norrving B, Pera J, Pichler A, Roquer J, Rosand J, Rost NS, Schmidt H, Schmidt R, Schwab K, Selim M, Silliman SL, Slowik A, Soriano C, Tirschwell DL, Urbanik A, Viswanathan A, Woo D, Worrall BBDigital Object Identifier: Date added to catalog: 2013-09-17
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article Available 22933587

Available online from MWHC library: 1970 - present, Available in print through MWHC library: 1999 - 2006

BACKGROUND AND PURPOSE: Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN.

CONCLUSIONS: Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN.

METHODS: We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables.

RESULTS: No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score.

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