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Catecholamine relea...
Catecholamine release-inhibitory peptide catestatin (chromogranin A352-372) : Naturally occurring amino acid variant Gly364Ser causes profound changes in human autonomic activity and alters risk for hypertension
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Rao, Fangwen (författare)
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Wen, Gen (författare)
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Gayen, Jiaur R. (författare)
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visa fler...
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Das, Madhusudan (författare)
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Vaingankar, Sucheta M. (författare)
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Rana, Brinda K. (författare)
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Mahata, Manjula (författare)
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Kennedy, Brian P. (författare)
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Salem, Rany M. (författare)
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- Stridsberg, Mats (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Clinical Chemistry
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Abel, Kenneth (författare)
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Smith, Douglas W. (författare)
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Eskin, Eleazar (författare)
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Schork, Nicholas J. (författare)
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Hamilton, Bruce A. (författare)
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Ziegler, Michael G. (författare)
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Mahata, Sushil K. (författare)
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O'Connor, Daniel T. (författare)
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(creator_code:org_t)
- 2007
- 2007
- Engelska.
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 115:17, s. 2271-2281
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- BACKGROUND - Chromogranin A, coreleased with catecholamines by exocytosis, is cleaved to the catecholamine release-inhibitory fragment catestatin. We identified a natural nonsynonymous variant of catestatin, Gly364Ser, that alters human autonomic function and blood pressure. METHODS AND RESULTS - Gly364Ser heterozygotes and controls underwent physiological and biochemical phenotyping, including catecholamine production, chromogranin A precursor, and its catestatin product. Case-control studies replicated effects of the gene on blood pressure in the population. Gly364Ser displayed diminished inhibition of catecholamine secretion from cultured neurons. Gly/Ser heterozygotes displayed increased baroreceptor slope during upward deflections (by ≈47%) and downward deflections (by ≈44%), increased cardiac parasympathetic index (by ≈2.4-fold), and decreased cardiac sympathetic index (by ≈26%). Renal norepinephrine excretion was diminished by ≈26% and epinephrine excretion by ≈34% in Gly/Ser heterozygotes. The coalescent dated emergence of the variant to ≈70 000 years ago. Gly364Ser was in linkage disequilibrium with 1 major Chromogranin A promoter haplotype, although promoter haplotypes did not predict autonomic phenotypes. The 364Ser variant was associated with lower diastolic blood pressure in 2 independent/confirmatory groups of patients with hypertension; genotype groups differed by ≈5 to 6 mm Hg, and the polymorphism accounted for ≈1.8% of population diastolic blood pressure variance, although a significant gene-by-sex interaction existed, with an enhanced effect in men. CONCLUSIONS - The catestatin Gly364Ser variant causes profound changes in human autonomic activity, both parasympathetic and sympathetic, and seems to reduce risk of developing hypertension, especially in men. A model for catestatin action in the baroreceptor center of the nucleus of the tractus solitarius accounts for these actions.
Nyckelord
- Acetylcholine
- Blood pressure
- Catecholamines
- Genetics
- Heart rate
- Hypertension
- Nervous system
- sympathetic
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Rao, Fangwen
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Wen, Gen
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Gayen, Jiaur R.
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Das, Madhusudan
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Vaingankar, Such ...
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Rana, Brinda K.
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visa fler...
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Mahata, Manjula
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Kennedy, Brian P ...
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Salem, Rany M.
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Stridsberg, Mats
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Abel, Kenneth
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Smith, Douglas W ...
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Eskin, Eleazar
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Schork, Nicholas ...
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Hamilton, Bruce ...
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Ziegler, Michael ...
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Mahata, Sushil K ...
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O'Connor, Daniel ...
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visa färre...
- Artiklar i publikationen
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Circulation
- Av lärosätet
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Uppsala universitet