Haplotypes of the Adrenergic System Predict the Blood Pressure Response to β-Blockers in Women with Essential Hypertension

Abstract

Aims: To analyze the association of haplotypes of the adrenergic system with essential hypertension and with the blood pressure response to β-blockers. Materials & methods: In 1112 never-treated essential hypertension patients and 203 normotensive controls, tightly linked SNPs of β-adrenergic receptors (ADRB1 – Ser49Gly and Arg389Gly; ADRB2 – Cys19Arg, Gly16Arg and Gln27Glu) and the G-protein β3-subunit (GNB3 – A3882C, G5249A and C825T) were genotyped. Association of haplotypes with essential hypertension and with the blood pressure response to atenolol 50 mg twice daily in a subgroup of essential hypertension patients (n = 340) was evaluated (Haploview 3.2). Results: No SNPs or haplotypes were associated with essential hypertension. In females only, GNB3 SNPs and haplotypes were associated with the blood pressure response (p < 0.05). Conclusion: Our study confirmed the sex-specific association of GNB3 with the blood pressure response to atenolol with no substantial advantage of the analysis of haplotypes over SNPs.

KEYWORDS::

• adrenergic antagonist
• genetics
• GNB3
• high blood pressure
• pharmacogenomics
• SNP

Acknowledgments

The authors are indebted to Cristina Barlassina, Department of Sciences and Biomedical Technologies, University of Milan, Milan, Italy, for her advice on genotyping.

Financial & competing interests disclosure

This work was supported in part by a Research Grant from the Italian Society of Hypertension (Fabiana Filigheddu), by the ‘Associazione per lo Sviluppo della Ricerca sull‘Ipertensione Arteriosa e sulle Malattie Cardiovascolari – ONLUS‘, Sassari, Italy (NG, CT) and by the Progetti di Educazione Sanitaria, Regione Sardegna, Italy (NG, CT). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported in part by a Research Grant from the Italian Society of Hypertension (Fabiana Filigheddu), by the ‘Associazione per lo Sviluppo della Ricerca sull‘Ipertensione Arteriosa e sulle Malattie Cardiovascolari – ONLUS‘, Sassari, Italy (NG, CT) and by the Progetti di Educazione Sanitaria, Regione Sardegna, Italy (NG, CT). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.