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CYP11B2 –344T/C Gene Polymorphism and Blood Pressure in Patients with Acromegaly

Division of Internal Medicine and Hypertension (P.Mu., F.V., G.L., C.C.), San Vito Hospital, and Medicina Interna I (S.B., F.D., A.A., M.T.), Dipartimento di Scienze Cliniche e Biologiche, S. Luigi Hospital, Orbassano, University of Torino, 10133 Torino, Italy; Clinica Medica III (P.Ma., C.M.), Dipartimento di Scienze Mediche e Chirurgiche, University of Padua, 35100 Padua, Italy; and Department of Biomedical Sciences and Advanced Therapies (M.B., E.C.d.U.), Section of Endocrinology, University of Ferrara, 44100 Ferrara, Italy

Address all correspondence and requests for reprints to: Paolo Mulatero, Hypertension Unit, Ospedale San Vito, Strada San Vito 34, 10133 Torino, Italy. E-mail: paolo.mulatero{at}libero.it.

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

Setting and Patients: We conducted a multicentric retrospective study that included 100 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 -adducin G460W polymorphisms.

Main Outcome Measure: We assessed the prevalence of hypertension and BP 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 (odds ratio = 4.0; 95% confidence interval = 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 systolic BP (10.2 ± 4.3 mm Hg; P = 0.02) but not a significant increase in diastolic BP (2.6 ± 2.6 mm Hg; P = 0.32) compared with patients with the CT/TT genotype.

Conclusions: We have shown an association of the –344T/C CYP11B2 gene polymorphism with BP in patients affected by acromegaly. These findings suggest that the RAAS is implicated in the pathogenesis of hypertension in acromegaly.