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(Hypertension. 1999;34:8-14.)
© 1999 American Heart Association, Inc.

Scientific Contribution

Association of the G_s Gene With Essential Hypertension and Response to ß-Blockade

Haiyan Jia; Aroon D. Hingorani; Pankaj Sharma; Ruth Hopper; Claire Dickerson; Debra Trutwein; Deborah D. Lloyd; Morris J. Brown

From the Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Correspondence to Dr Haiyan Jia, Wolfson Institute for Biomedical Research (formerly Cruciform Project), Rayne Institute, University College London, 5 University St, London WC1E 6JJ, UK. E-mail h.jia{at}ucl.ac.uk

Abstract—We examined whether the GNAS1 locus, encoding the G_s protein -subunit (G_s), is implicated in the genetic causes of essential hypertension. A common silent polymorphism (ATTATC, Ile¹³¹) was identified in exon 5 of the G_s gene by single-strand conformation polymorphism analysis and DNA sequencing. This polymorphism consists of the presence (+) or absence (-) of a restriction site for FokI. Only 1 other rare allele was found in the coding region; the high GC content of the 5' noncoding sequence prevented mutation scanning of the promoter region of the gene. There was a significant difference in frequency of the FokI alleles between 268 white hypertensives (FokI+:FokI-, 51%:49%) and a matched group of 231 control subjects (FokI+:FokI-, 58%:42%) (P=0.02). Multiple regression analysis showed that the FokI genotype was independently related to the level of untreated systolic blood pressure in 294 well-characterized white hypertensives (P=0.01) but not in normotensives. The influence of the FokI allele on blood pressure (BP) response to ß-blockade was examined in 114 of the patients randomly assigned to this class of drug. Significant differences in frequency of the FokI allele were observed in the good responders (FokI+:FokI-, 62.5%:37.5%, n=36) versus the poor responders (FokI+:FokI-, 41.7%:58.3%, n=30) after ß-blocker therapy (P=0.02). In a multiple regression analysis, the G_s genotype was the only independent predictor of BP response. These results suggest that the GNAS1 locus might carry a functional variant that influences BP variation and response to ß-blockade in essential hypertension.

Key Words: G proteins • hypertension, essential • genetics • polymorphism

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