A polymorphism of the α-subunit of adducin, Gly460→Trp, may affect membrane ion transport and be associated with human EH (essential hypertension). The α-adducin Gly460→Trp polymorphism was determined in 242 NC (normal controls) and 73 patients with EH and was related to the membrane ion transport marker in EH, erythrocyte Na/LiCT (sodium–lithium countertransport), in a subgroup of these subjects. The Km for external sodium was lower in patients with EH than NC. The Km of the Trp allele was lower than with the Gly/Gly genotype [NC, 105±6 compared with 88±5 mmol Na/l respectively (P=0.05); patients with EH, 76±5 compared with 64±4 mmol Na/l respectively (P=0.06)]. The Km was lower in patients with EH than NC for any adducin genotype. Thiol alkylation with NEM (N-ethylmaleimide) caused a decrease in Km in NC, but not in patients with EH. With a Trp allele, NEM lowered Km less in NC (−20 compared with −35) and increased it in patients with EH (+24 compared with +3; P=0.007 for genotype effect). Thiol alkylation with NEM caused an increase in Vmax in patients with EH but not in NC. With a Trp allele, NEM increased Vmax substantially in patients with EH (+0.12 compared with +0.03) but did not cause a decrease in NC (+0.02 compared with −0.06; P=0.007 for genotype effect). In conclusion, the Gly460→Trp polymorphism of α-adducin modifies the kinetics of Na/LiCT. The effect of this genotype is different in patients with EH compared with NC and it does not explain the abnormal kinetics in patients with EH. The Trp allele was not associated with disease in the population studied. Several cytoskeletal proteins may interact with adducin in the overall phenotype of EH.
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March 2005
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Research Article|
February 18 2005
Sodium–lithium countertransport and the Gly460→Trp α-adducin polymorphism in essential hypertension
Paul A. MEAD;
Paul A. MEAD
*Department of Nephrology, Cumberland Infirmary, Carlisle CA2 7HY, U.K.
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John N. HARVEY;
John N. HARVEY
†University of Wales College of Medicine, Maelor Hospital, Wrexham, Clwyd LL13 7TD, U.K.
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Peter A. RUTHERFORD;
Peter A. RUTHERFORD
†University of Wales College of Medicine, Maelor Hospital, Wrexham, Clwyd LL13 7TD, U.K.
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Helen LEITCH;
Helen LEITCH
†University of Wales College of Medicine, Maelor Hospital, Wrexham, Clwyd LL13 7TD, U.K.
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Trevor H. THOMAS
‡School of Clinical Medical Sciences, University of Newcastle-upon-Tyne, Newcastle-upon-Tyne NE2 4HH, U.K.
Correspondence: Dr Trevor H. Thomas (email [email protected]).
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Publisher: Portland Press Ltd
Received:
September 06 2004
Revision Received:
October 20 2004
Accepted:
November 19 2004
Accepted Manuscript online:
November 19 2004
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society
2005
Clin Sci (Lond) (2005) 108 (3): 231–236.
Article history
Received:
September 06 2004
Revision Received:
October 20 2004
Accepted:
November 19 2004
Accepted Manuscript online:
November 19 2004
Citation
Paul A. MEAD, John N. HARVEY, Peter A. RUTHERFORD, Helen LEITCH, Trevor H. THOMAS; Sodium–lithium countertransport and the Gly460→Trp α-adducin polymorphism in essential hypertension. Clin Sci (Lond) 1 March 2005; 108 (3): 231–236. doi: https://doi.org/10.1042/CS20040267
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