Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage

作者：Falcone Guido J; Biffi Alessandro; Devan William J; Jagiella Jeremiasz M; Schmidt Helena; Kissela Brett; Hansen Bjoern M; Jimenez Conde Jordi; Giralt Steinhauer Eva; Elosua Roberto; Cuadrado Godia Elisa; Soriano Carolina; Ayres Alison M; Schwab Kristin; Pera Joanna; Urbanik Andrzej; Rost Natalia S; Goldstein Joshua N; Viswanathan Anand; Pichler Alexander; Enzinger Christian; Norrving Bo; Tirschwell David L; Selim Magdy; Brown Devin L; Silliman Scott L

来源：Stroke, 2012, 43(11): 2877-U183.

DOI：10.1161/STROKEAHA.112.659755

• genetic risk score
• genetics
• hypertension
• intracerebral hemorrhage

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;Conclusion-Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN. (Stroke. 2012; 43: 2877-2883.)

• 出版日期2012-11