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This version published online on September 26, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-0049
A more recent version of this article appeared on December 1, 2006
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Submitted on January 10, 2006
Accepted on September 15, 2006

CYP11B2 -344T/C GENE POLYMORPHISM AND BLOOD PRESSURE IN PATIENTS WITH ACROMEGALY

Paolo Mulatero*, Franco Veglio, Pietro Maffei, Marta Bondanelli, Silvia Bovio, Fulvia Daffara, Giannina Leotta, Alberto Angeli, Chiara Calvo, Chiara Martini, Ettore C. degli Uberti, and Massimo Terzolo

Division of Internal Medicine and Hypertension, San Vito Hospital, Torino, and Medicina Interna I, Dipartimento di Scienze Cliniche e Biologiche, S. Luigi Hospital, Orbassano, University of Torino; Clinica Medica III, Dipartimento di Scienze Mediche e Chirurgiche, University of Padua, Department of Biomedical Sciences and Advanced Therapies, Section of Endocrinology, University of Ferrara, Italy

* To whom correspondence should be addressed. E-mail: paolo.mulatero{at}libero.it.

Context: the pathogenesis of increased blood pressure levels (BP) in acromegaly is unclear and the role of IGF-I levels and the renin-angiotensin-aldosterone system (RAAS) in this disease remain controversial.

Objective and design: the aim of this study was to investigate the role of gene polymorphisms of the RAAS and involved in sodium handling on BP levels in acromegaly.

Setting: multicentric retrospective study.

Patients: one hundred consecutive patients with acromegaly referred during the period 2000-2003.

Intervention: all patients were genotyped for ACE I/D, AGT M235T, CYP11B2 -344T/C, B2R -58T/C and {alpha}-adducin G460W polymorphisms.

Main outcome measure: prevalence of hypertension and BP levels according to the genotype.

Results: patients with the CYP11B2 -344CC genotype displayed a significant increase in the risk of hypertension compared with patients with CT/TT genotypes (OR= 4.0, 95% CI 1.4-11.6, P = 0.01). Consistently, a significant proportion of patients with the CYP11B2 -344CC genotypes were under antihypertensive treatment (73.1%) compared with patients with the TT/TC genotypes (38.2%, P = 0.003). Patients with the -344CC genotype displayed a significant increase in SBP levels (10.2 ± 4.3 mmHg, P = 0.02) but not a significant increase in DBP levels (2.6 ± 2.6 mmHg, P = 0.32) compared with patients with the CT/TT genotype.

Conclusions: we have shown an association of the -344T/C CYP11B2 gene polymorphism to BP levels in patients affected by acromegaly. These findings suggest that the RAAS system is implicated in the pathogenesis of hypertension in acromegaly.
Key words: acromegaly • genetic polymorphisms • renin-angiotensin system • IGF-I • aldosterone synthase






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