Pleiotropic effects of novel trans-acting loci influencing human sympathochromaffin secretion.

Pleiotropic effects of novel trans-acting loci influencing human sympathochromaffin secretion. Research Abstract Details 

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Pleiotropic effects of novel trans-acting loci influencing human sympathochromaffin secretion. Abstract Text:

Tiffany A Greenwood,Fangwen Rao,Mats Stridsberg,Nitish R Mahapatra,Manjula Mahata,Elizabeth O Lillie,Sushil K Mahata,Laurent Taupenot,Nicholas J Schork,Daniel T O'Connor,

Family studies have suggested a genetic contribution to variation in blood pressure, but the genes responsible have thus far eluded identification. The use of intermediate phenotypes associated with hypertension, such as chromogranin plasma concentrations, may assist the discovery of hypertension-predisposing loci. We measured the concentrations of four chromogranin A (CHGA) and B (CHGB) peptides in 742 individuals from 235 nuclear families. The CHGA- and CHGB-derived peptides displayed significant heritability and revealed significant genetic correlations, most strikingly observed between CHGA(361-372) (catestatin) and CHGB(439-451). A 5-cM microsatellite genome scan revealed significant and suggestive evidence for linkage on several chromosomes for three of the peptides. Subsequent bivariate linkage analysis for peptides CHGA(361-372) and CHGB(439-451), which showed evidence for convergent linkage peaks on chromosomes 2, 7, and 13, resulted in increased evidence for linkage to these regions, suggesting pleiotropic effects of these three loci on multiple chromogranin traits. Because CHGA itself is on chromosome 14q32, and CHGB itself is on chromosome 20pter-p12, the pleiotropic regions on chromosomes 2, 7, and 13 must represent trans-acting quantitative trait loci coordinately affecting CHGA/CHGB biosynthesis and/or exocytotic secretion, likely by regulating efferent sympathetic outflow, a conclusion consistent with the in vitro studies presented here of the dual control of both exocytosis and transcription of these peptides by secretory stimuli in chromaffin cells. The results suggest a new approach to heritable autonomic control of circulation and the genetic basis of cardiovascular diseases such as systemic hypertension.

Pleiotropic effects of novel trans-acting loci influencing human sympathochromaffin secretion. Publishing Authors By Initials

TA Greenwood,F Rao,M Stridsberg,NR Mahapatra,M Mahata,EO Lillie,SK Mahata,L Taupenot,NJ Schork,DT O'Connor,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Pleiotropic effects of novel trans-acting loci influencing human sympathochromaffin secretion. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Physiological genomics

VOLUME: 25

Page Numbers: 470-9

Journal Abbreviation: Physiol. Genomics

ISSN: 1531-2267

DAY: 22

MONTH: 03

YEAR: 2006

Pleiotropic effects of novel trans-acting loci influencing human sympathochromaffin secretion. Information

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LANGUAGE: eng

NlmUniqueID: 9815683

Pleiotropic effects of novel trans-acting loci influencing human sympathochromaffin secretion. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: genetics

Chemical & Substance for Abstract: Pleiotropic effects of novel trans-acting loci influencing human sympathochromaffin secretion. Information

Substance Name: Nicotine

Registry Number: 54-11-5

Grant and Affiliation Information for Pleiotropic effects of novel trans-acting loci influencing human sympathochromaffin secretion.

AFFILIATION: Department of Medicine, University of California-San Diego, La Jolla, USA.

Country: United States

AGENCY: United States NCRR

GRANT: RR-00827

ACRONYM: RR

MEDLINETA: Physiol Genomics

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