Document Detail


Two point mutations within the adducin genes are involved in blood pressure variation.
MedLine Citation:
PMID:  8171025     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Milan hypertensive strain of rats (MHS) develops a genetic form of renal hypertension that, when compared to its normotensive control (MNS), shows renal dysfunction similar to that of a subset of human patients with primary hypertension. MHS and MNS were shown to be homozygous by multilocus minisatellite analysis and monolocus microsatellite markers. We show here that one point mutation in each of two genes coding for the membrane skeleton protein adducin is associated with blood pressure in the Milan strain of rats. Adducin is a heterodimer formed by alpha and beta subunits that promotes the assembly of actin with spectrin. MHS and MNS differ, respectively, by the amino acids Y and F at position 316 of the alpha subunit. In the beta-adducin locus, MHS is always homozygous for R at position 529 while in MNS either R or Q occurs in that position. The R/Q heterozygotes showed lower blood pressure than any of the homozygotes. In vitro phosphorylation studies suggest that both of these amino acid substitutions occur within protein kinase recognition sites. Analysis of an F2 generation demonstrated that Y alleles segregated with a significant increment in blood pressure. This effect is modulated by the presence of the R allele of the beta subunit. Taken together, these findings strongly support a role for adducin polymorphisms in causing variation of blood pressure in the Milan strain of rats.
Authors:
G Bianchi; G Tripodi; G Casari; S Salardi; B R Barber; R Garcia; P Leoni; L Torielli; D Cusi; M Ferrandi
Related Documents :
16272955 - The role of the cytochrome p450 3a5 enzyme for blood pressure regulation in the general...
14647005 - Associations between the human insulin gene 5' vntr and clinical variables of the renin...
16685205 - Functional variants of the angiotensinogen gene determine antihypertensive responses to...
9147895 - Insertion/deletion polymorphism in the angiotensin-converting-enzyme gene and blood pre...
22835615 - Use of continuous positive airway pressure reduces airway reactivity in adults with ast...
17946185 - Reflectance forehead pulse oximetry: effects of contact pressure during walking.
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  91     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1994 Apr 
Date Detail:
Created Date:  1994-06-01     Completed Date:  1994-06-01     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3999-4003     Citation Subset:  IM    
Affiliation:
Nephrology Clinic, University of Milan, San Raffaele Hospital, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Base Sequence
Blood Pressure*
Calmodulin-Binding Proteins / genetics*
DNA Primers / chemistry
Female
Heterozygote
Hypertension / genetics*
Male
Molecular Sequence Data
Peptides / chemistry
Phosphoproteins / metabolism
Phosphorylation
Polymorphism, Genetic
Rats
Chemical
Reg. No./Substance:
0/Calmodulin-Binding Proteins; 0/DNA Primers; 0/Peptides; 0/Phosphoproteins; 0/adducin
Comments/Corrections

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


Previous Document:  Canine X chromosome-linked hereditary nephritis: a genetic model for human X-linked hereditary nephr...
Next Document:  Consistent intergenic splicing and production of multiple transcripts between AML1 at 21q22 and unre...