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Common genetic variation in the type A endothelin-1 receptor is associated with ambulatory blood pressure: A family study

Lookup NU author(s): Dr Thahira Rahman, Michelle Baker, Dr Darroch Hall, Dr Peter Avery, Professor Bernard Keavney

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Abstract

The endothelins are among the most potent vasoconstrictors known. Pharmacological inhibition of endothelin receptors lowers blood pressure (BP). It is unknown whether naturally occurring genetic variation in the endothelin receptors influences BP. We have evaluated the type A endothelin receptor (EDNRA) as a candidate gene for hypertension in a large family study. A total of 1425 members of 248 families selected via a proband with hypertension were studied. Ambulatory BP monitoring was conducted using the A&D TM2421 device. Four haplotype-tagging single nucleotide polymorphisms (SNPs) spanning the EDNRA gene were typed. There was evidence of association between genotype at the rs5335 (C + 70G) SNP and night systolic blood pressure (+1.24% (s.e. 0.64) per G allele; P = 0.05); night diastolic blood pressure (+1.64% (s.e. 0.71) per G allele; P = 0.021) and night mean BP (+1.51% (s.e. 0.64) per G allele; P = 0.017). Borderline significant trends in the same direction were seen for daytime BPs. Proportions of hypertensives in each of the three genotype groups were C/C 34.7%, C/G 37.9%, G/G 42.4% yielding an odds ratio for hypertension per G allele of 1.19 (95% confidence interval 1.00-1.41; P = 0.05). In conclusion, the rs5335 (C + 70G) polymorphism of the EDNRA gene has small effects on the risk of hypertension. Natural variation in other genes in the endothelin-signalling pathway should be explored to identify additional influences on BP regulation.


Publication metadata

Author(s): Rahman T, Baker M, Hall DH, Avery PJ, Keavney B

Publication type: Article

Publication status: Published

Journal: Journal of Human Hypertension

Year: 2008

Volume: 22

Issue: 4

Pages: 282-288

Print publication date: 01/04/2008

ISSN (print): 0950-9240

ISSN (electronic):

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.jhh.1002322

DOI: 10.1038/sj.jhh.1002322

PubMed id: 18172451


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