This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jia, H. Articles by Brown, M. J. Search for Related Content PubMed PubMed Citation Articles by Jia, H. Articles by Brown, M. J. Pubmed/NCBI databases OMIM Medline Plus Health Information High Blood Pressure Related Collections Cardiovascular Pharmacology Other hypertension Genetics of cardiovascular disease

(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

This article has been cited by other articles:

				Y.-M. Mao, Z.-Q. Liu, B.-L. Chen, D. Guo, C.-T. Han, L.-J. Yang, S.-Y. Wang, L. Fan, and H.-H. Zhou Effect of 393T>C Polymorphism of GNAS1 Gene on Dobutamine Response in Chinese Healthy Subjects J. Clin. Pharmacol., August 1, 2009; 49(8): 929 - 936. [Abstract] [Full Text] [PDF]

				H. A. Ghofrani, R. J. Barst, R. L. Benza, H. C. Champion, K. A. Fagan, F. Grimminger, M. Humbert, G. Simonneau, D. J. Stewart, C. Ventura, et al. Future perspectives for the treatment of pulmonary arterial hypertension. J. Am. Coll. Cardiol., June 30, 2009; 54(1 Suppl): S108 - S117. [Abstract] [Full Text] [PDF]

				M. Lelonek, T. Pietrucha, M. Matyjaszczyk, and J. H. Goch A novel approach to syncopal patients: association analysis of polymorphisms in G-protein genes and tilt outcome Europace, January 1, 2009; 11(1): 89 - 93. [Abstract] [Full Text] [PDF]

				D. Rosskopf and M. C. Michel Pharmacogenomics of G Protein-Coupled Receptor Ligands in Cardiovascular Medicine Pharmacol. Rev., December 1, 2008; 60(4): 513 - 535. [Abstract] [Full Text] [PDF]

				B. C. Rossier and L. Schild Epithelial Sodium Channel: Mendelian Versus Essential Hypertension Hypertension, October 1, 2008; 52(4): 595 - 600. [Full Text] [PDF]

				S. J. Lee, J. Liu, A. M. Westcott, J. A. Vieth, S. J. DeRaedt, S. Yang, B. Joe, and G. T. Cicila Substitution Mapping in Dahl Rats Identifies Two Distinct Blood Pressure Quantitative Trait Loci Within 1.12- and 1.25-Mb Intervals on Chromosome 3 Genetics, December 1, 2006; 174(4): 2203 - 2213. [Abstract] [Full Text] [PDF]

				S. Hahn, U. H Frey, W. Siffert, S. Tan, K. Mann, and O. E Janssen The CC genotype of the GNAS T393C polymorphism is associated with obesity and insulin resistance in women with polycystic ovary syndrome. Eur. J. Endocrinol., November 1, 2006; 155(5): 763 - 770. [Abstract] [Full Text] [PDF]

				S. Padmanabhan, C. Wallace, P. B. Munroe, R. Dobson, M. Brown, N. Samani, D. Clayton, M. Farrall, J. Webster, M. Lathrop, et al. Chromosome 2p Shows Significant Linkage to Antihypertensive Response in the British Genetics of Hypertension Study Hypertension, March 1, 2006; 47(3): 603 - 608. [Abstract] [Full Text] [PDF]

				T. Nieminen, T. Lehtimaki, J. Laiho, R. Rontu, K. Niemela, T. Koobi, R. Lehtinen, J. Viik, V. Turjanmaa, and M. Kahonen Effects of polymorphisms in beta1-adrenoceptor and {alpha}-subunit of G protein on heart rate and blood pressure during exercise test. The Finnish Cardiovascular Study J Appl Physiol, February 1, 2006; 100(2): 507 - 511. [Abstract] [Full Text] [PDF]

				J. A. Johnson and L. H. Cavallari Cardiovascular pharmacogenomics Exp Physiol, May 1, 2005; 90(3): 283 - 289. [Abstract] [Full Text] [PDF]

				U. H. Frey, A. Eisenhardt, G. Lummen, H. Rubben, K.-H. Jockel, K. W. Schmid, and W. Siffert The T393C Polymorphism of the G{alpha}s Gene (GNAS1) Is a Novel Prognostic Marker in Bladder Cancer Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 871 - 877. [Abstract] [Full Text] [PDF]

				G. H. Gibbons, C. C. Liew, M. O. Goodarzi, J. I. Rotter, W. A. Hsueh, H. M. Siragy, R. Pratt, and V. J. Dzau Genetic Markers: Progress and Potential for Cardiovascular Disease Circulation, June 29, 2004; 109(25_suppl_1): IV-47 - IV-58. [Full Text] [PDF]

				S. L. Kirstein and P. A. Insel Autonomic Nervous System Pharmacogenomics: A Progress Report Pharmacol. Rev., March 1, 2004; 56(1): 31 - 52. [Abstract] [Full Text] [PDF]

				W E Evans Pharmacogenomics: marshalling the human genome to individualise drug therapy Gut, May 1, 2003; 52(90002): ii10 - 18. [Abstract] [Full Text]

				M. Abe, J. Nakura, M. Yamamoto, J. J. Jin, Z. Wu, Y. Tabara, Y. Yamamoto, M. Igase, K. Kohara, and T. Miki Association of GNAS1 Gene Variant With Hypertension Depending on Smoking Status Hypertension, September 1, 2002; 40(3): 261 - 265. [Abstract] [Full Text] [PDF]

				N. Glorioso, F. Filigheddu, D. Cusi, C. Troffa, M. Conti, M. Natalizio, G. Argiolas, C. Barlassina, and G. Bianchi {alpha}-Adducin 460Trp Allele Is Associated With Erythrocyte Na Transport Rate in North Sardinian Primary Hypertensives Hypertension, February 1, 2002; 39(2): 357 - 362. [Abstract] [Full Text] [PDF]

				C. A. Ladines, C. Zeng, L. D. Asico, X. Sun, F. Pocchiari, C. Semeraro, J. Pisegna, S. Wank, I. Yamaguchi, G. M. Eisner, et al. Impaired renal D1-like and D2-like dopamine receptor interaction in the spontaneously hypertensive rat Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2001; 281(4): R1071 - R1078. [Abstract] [Full Text] [PDF]

				R. S. Ostrom, S. R. Post, and P. A. Insel Stoichiometry and Compartmentation in G Protein-Coupled Receptor Signaling: Implications for Therapeutic Interventions Involving Gs J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 407 - 412. [Abstract] [Full Text]