Document Detail

Corin I555(P568) allele is associated with enhanced cardiac hypertrophic response to increased systemic afterload.
MedLine Citation:
PMID:  17296875     Owner:  NLM     Status:  MEDLINE    
Corin activates pro-A-type naturetic peptide and pro-B-type naturetic peptide into biologically active molecules. We recently identified a minor allele in the corin gene defined by 2 highly linked single nucleotide polymorphisms (T555I and Q568P), which was associated with hypertension in blacks. Because of the direct antihypertrophic effects of the natriuretic peptide system, we hypothesized that the minor corin I555(P568) allele would be associated with an enhanced hypertrophic response to pressure overload. The relationship between systolic blood pressure and indexed left ventricular mass, derived from cardiac MRI, was analyzed in the Dallas Heart Study as a function of corin allele status. The Multi-Ethnic Study of Atherosclerosis was used as a validation cohort. All of the analyses were limited to self-identified blacks without treatment for hypertension. In addition, we genotyped 2114 markers highly informative for African ancestry in the Dallas Heart Study and derived a covariate representing African ancestry for multivariate models. In adjusted analysis, the corin I555(P568) allele was an independent predictor of left-ventricular mass in subjects with elevated systolic blood pressure. Linear spline regression analysis confirmed a significant interaction (P=0.002) between the corin I555(P568) allele and systolic blood pressure as a predictor of left ventricular mass in subjects with systolic blood pressure >120 mm Hg, and this nonlinear interaction was replicated in the Multi-Ethnic Study of Atherosclerosis. In the Dallas Heart Study, the corin I555(P568) allele was also associated with an increased odds for prevalent left ventricular hypertrophy in the presence of untreated hypertension. These data suggest that the corin I555(P568) allele represents a cardiac hypertrophy-sensitizing genetic locus in systemic hypertension.
J Eduardo Rame; Mark H Drazner; Wendy Post; Ronald Peshock; Joao Lima; Richard S Cooper; Daniel L Dries
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-02-12
Journal Detail:
Title:  Hypertension     Volume:  49     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-22     Completed Date:  2007-04-05     Revised Date:  2010-06-04    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  857-64     Citation Subset:  IM    
Division of Cardiology, University of California San Francisco, USA.
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MeSH Terms
Blood Pressure
Cohort Studies
Hypertension / complications*,  physiopathology
Hypertrophy, Left Ventricular / epidemiology,  etiology*,  genetics*,  physiopathology
Magnetic Resonance Imaging
Middle Aged
Polymorphism, Single Nucleotide*
Serine Endopeptidases / genetics*
Grant Support
K23-HL04455/HL/NHLBI NIH HHS; N01-HC-95159/HC/NHLBI NIH HHS; N01-HC-95160/HC/NHLBI NIH HHS; N01-HC-95161/HC/NHLBI NIH HHS; N01-HC-95162/HC/NHLBI NIH HHS; N01-HC-95163/HC/NHLBI NIH HHS; N01-HC-95164/HC/NHLBI NIH HHS; N01-HC-95165/HC/NHLBI NIH HHS; N01-HC-95169/HC/NHLBI NIH HHS; R0-1 45508//PHS HHS; R0-1 47910//PHS HHS
Reg. No./Substance:
EC 3.4.21.-/CORIN protein, human; EC 3.4.21.-/Serine Endopeptidases
Comment In:
Hypertension. 2007 Apr;49(4):765-6   [PMID:  17309958 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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