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Association of ATP1A1 and dear single-nucleotide polymorphism haplotypes with essential hypertension

Glorioso, Nicola and Herrera, Victoria L. M. and Bagamasbad, Pia and Filigheddu, Fabiana and Troffa, Chiara and Argiolas, Giuseppe and Bulla, Emanuela and Decano, Julius L. and Ruiz-Opazo, Nelson (2007) Association of ATP1A1 and dear single-nucleotide polymorphism haplotypes with essential hypertension. Circulation Research, Vol. 100 (10), p. 1522-1529. eISSN 1524-4571. Article.

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DOI: 10.1161/01.RES.0000267716.96196.60


Essential hypertension remains a major risk factor for cardiovascular and cerebrovascular diseases. As a complex multifactorial disease, elucidation of susceptibility loci remains elusive. ATP1A1 and Dear are candidate genes for 2 closely linked rat chromosome-2 blood pressure quantitative trait loci. Because corresponding human syntenic regions are on different chromosomes, investigation of ATP1A1 (chromosome [chr]-1p21) and Dear (chr-4q31.3) facilitates genetic analyses of each blood pressure quantitative trait locus in human hypertension. Here we report the association of human ATP1A1 (P<0.000005) and Dear (P<0.03) with hypertension in a relatively isolated, case/control hypertension cohort from northern Sardinia by single-nucleotide polymorphism haplotype analysis. Sex-specific haplotype analyses detected stronger association of both loci with hypertension in males than in females. Haplotype trend-regression analyses support ATP1A1 and Dear as independent susceptibility loci and reveal haplotype-specific association with hypertension and normotension, thus delineating haplotype-specific subsets of hypertension. Although investigation in other cohorts needs to be performed to determine genetic effects in other populations, haplotype subtyping already allows systematic stratification of susceptibility and, hence, clinical heterogeneity, a prerequisite for unraveling the polygenic etiology and polygene–environment interactions in essential hypertension. As hypertension susceptibility genes, coexpression of ATP1A1 and Dear in both renal tubular cells and vascular endothelium suggest a cellular pathogenic scaffold for polygenic mechanisms of hypertension, as well as the hypothesis that ATP1A1 and/or Dear could contribute to the known renal and vascular endothelial dysfunction associated with essential (polygenic) hypertension.

Item Type:Article
ID Code:766
Uncontrolled Keywords:α1Na,K-ATPase, Dear, hypertension, genetics, risk factor
Subjects:Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 03 Istituti > Clinica medica generale e terapia medica
002 Altri enti e centri di ricerca del Nord Sardegna > Azienda ASL1, Sassari > Centro prevenzione, diagnosi e terapia dell'ipertensione arteriosa e delle complicanze cardiovascolari
Publisher:Lippincott Williams & Wilkins
Copyright Holders:© 2007 American Heart Association
Deposited On:18 Aug 2009 10:03

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