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Sodium-lithium countertransport and the Gly460 → Trp α-adducin polymorphism in essential hypertension

Lookup NU author(s): Dr Trevor Thomas

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Abstract

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 K m 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. © 2005 The Biochemical Society.


Publication metadata

Author(s): Mead PA, Harvey JN, Rutherford PA, Leitch H, Thomas TH

Publication type: Article

Publication status: Published

Journal: Clinical Science

Year: 2005

Volume: 108

Issue: 3

Pages: 231-236

ISSN (print): 0143-5221

ISSN (electronic): 1470-8736

Publisher: Portland Press Ltd.

URL: http://dx.doi.org/10.1042/CS20040267

DOI: 10.1042/CS20040267

PubMed id: 15554870


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