Human Molecular Genetics, Vol 6, 1527-1534, Copyright © 1997 by Oxford University Press
A Knoll, H Schunkert, K Reichwald, AH Danser, D Bauer, M Platzer, G Stein and A Rosenthal
The role of renin binding protein (RnBP) in human (patho)physiology,
despite its biochemical characterization, is as yet unclear. RnBP has been
shown to bind and inactivate renin, a key player of the blood pressure
regulating renin-angiotensin system. This renders the RnBP gene a promising
candidate gene in human hypertension. Herein, a molecular genetic approach
was employed to investigate if RnBP might affect renin, prorenin and/or
blood pressure levels. Sequencing of the human Xq28 chromosomal region
provided the precise chromosomal location and full genomic sequence of the
RnBP gene. All 11 exons, adjacent intronic splice sites and the promoter
region were sequenced in 20 patients with essential hypertension of early
onset and possible X- linked inheritance and in four normotensive
individuals. The only variant found was a single base exchange polymorphism
61 base pairs upstream of the intron 6/exon 7 boundary (T61C). Several
cardiovascular parameters, the renin, and prorenin levels and the T61C
allele status were determined in 505 Caucasian individuals. Male
individuals without medication who were hemizygous for the C allele were
characterized by lower prorenin levels (196 +/- 15 versus 256 +/- 12 mU/l,
P = 0.05) and a significantly higher renin/prorenin ratio (10.7 +/- 1.5
versus 7.7 +/- 0.3%, P = 0.002), whereas no variations in circulating
renin, blood pressure, heart rate and left ventricular mass index were
associated with the C allele. No significant association was observed in
women. The data do not exclude a role of RnBP in essential hypertension.
The complete genomic structure of the RnBP gene, including the identified
repetitive sequence elements, provides an essential tool for further
studies of the RnBP gene in hypertensive patients with a different genetic
background.
ARTICLES
Human renin binding protein: complete genomic sequence and association of an intronic T/C polymorphism with the prorenin level in males
Department of Pathology, University of Regensburg, Germany.
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