|
|
 Previous Article | Table of Contents | Next Article 
Antithrombin III Nagasaki (Ser116-Pro): a heterozygous variant with
defective heparin binding associated with thrombosis
K Okajima, H Abe, S Maeda, M Motomura, M Tsujihata, S Nagataki, H Okabe and K Takatsuki
Department of Laboratory Medicine, Kumamoto University Medical School,
Japan.
A novel variant of antithrombin III (AT III) that lacks affinity for
heparin was found in a 33-year-old man who suffered from recurrent cerebral
infarction. The propositus had a history of recurrent ischemic attacks from
the age of 28. He was obese and had a smoking habit (30 to 40
cigarettes/day), low high-density lipoprotein cholesterol, and a mild
glucose intolerance as the possible risk factors for thrombosis. No family
history of thromboembolic episodes was observed. Coagulation studies found
low heparin cofactor activity (55%) of AT III, with a normal immunoreactive
level (109.7%) and progressive antithrombin activity (117%). Other factors
capable of predisposing him to hereditary thrombophilia were within normal
ranges. Analysis by crossed immunoelectrophoresis in the presence of
heparin and affinity chromatography on heparin-Sepharose demonstrated that
the propositus' AT III was composed of two populations, one having no
affinity for heparin and the other binding heparin normally. Nucleotide
sequencing of 7 exons of the propositus' AT III gene using polymerase chain
reaction and subcloning disclosed a transition of thymine to cytosine in
exon 3a (codon 116) of the AT III gene leading to a Ser116-Pro conversion.
Allele-specific oligonucleotide hybridization procedures confirmed the
presence of the mutation in the propositus' genomic DNA. Using the same
technique, the mutation was also found in his father's genomic DNA, but not
in that of his mother. These findings indicate that Ser116 is an important
amino acid residue in heparin binding and that the propositus is
heterozygous for the abnormality. Furthermore, the fact that the propositus
suffered from recurrent cerebral infarction suggested that being
heterozygous for a heparin-binding defect would lead to a predisposition to
thrombosis when associated with various risk factors. The name AT III
Nagasaki is proposed for this variant AT III containing a novel Ser116-Pro
mutation.
Volume 81,
Issue 5,
pp. 1300-1305,
03/01/1993
Copyright © 1993 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
N. Paredes, A. Wang, L. R. Berry, L. J. Smith, A. R. Stafford, J. I. Weitz, and A. K. C. Chan
Mechanisms Responsible for Catalysis of the Inhibition of Factor Xa or Thrombin by Antithrombin Using a Covalent Antithrombin-Heparin Complex
J. Biol. Chem.,
June 20, 2003;
278(26):
23398 - 23409.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Jairajpuri, A. Lu, U. Desai, S. T. Olson, I. Bjork, and S. C. Bock
Antithrombin III Phenylalanines 122 and 121 Contribute to Its High Affinity for Heparin and Its Conformational Activation
J. Biol. Chem.,
April 25, 2003;
278(18):
15941 - 15950.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Mizutani, K. Okajima, M. Uchiba, H. Isobe, N. Harada, S. Mizutani, and T. Noguchi
Antithrombin reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation through promotion of prostacyclin production
Blood,
April 15, 2003;
101(8):
3029 - 3036.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Belzar, A. Zhou, R. W. Carrell, P. G. W. Gettins, and J. A. Huntington
Helix D Elongation and Allosteric Activation of Antithrombin
J. Biol. Chem.,
March 1, 2002;
277(10):
8551 - 8558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Isobe, K. Okajima, M. Uchiba, N. Harada, and H. Okabe
Antithrombin prevents endotoxin-induced hypotension by inhibiting the induction of nitric oxide synthase in rats
Blood,
March 1, 2002;
99(5):
1638 - 1645.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Harada, K. Okajima, S. Kushimoto, H. Isobe, and K. Tanaka
Antithrombin Reduces Ischemia/Reperfusion Injury of Rat Liver by Increasing the Hepatic Level of Prostacyclin
Blood,
January 1, 1999;
93(1):
157 - 164.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
