CYP11B2 -344T/C gene polymorphism and blood pressure in patients with acromegaly.

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 alpha-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.

Autonomic neuropathy and QT interval in hemodialysed patients.

BACKGROUND: QT interval prolongation increases the risk of ventricular arrhythmias and sudden death in diabetic autonomic neuropathy and ischemic heart disease. In end-stage renal disease (ESRD), the effects of hemodialysis on QT interval are diverse and the influence of autonomic neuropathy has yet to be clearly defined. METHODS: Sixty-nine ERSD patients (age 64 +/- 14) were studied. Prior to the dialysis session, patients underwent four standard autonomic cardiovascular tests; before and after the dialysis session, a 12-lead ECG was recorded. Corrected QT intervals (QTc) were measured and QT dispersion (QTd) was calculated. Twelve subjects (age 59 +/- 6) with normal renal function served as control group. RESULTS: Compared to controls, ESRD patients showed a longer QTc (434 +/- 26 vs 414 +/- 28 ms; p = 0.016) and a similar QTd (35 +/- 13 vs 37 +/- 14 ms; p = 0.54).QTc was > 440 ms in 33.3% of the patients. No difference in the prevalence or score of autonomic neuropathy was observed between the subgroups with and without a prolonged QTc. After the hemodialysis session, QTc increased in 56% and decreased in 43% of the patients, and QTd increased in 45 % and decreased in 55% of the patients. QTc and QTd changes were not related to the presence of autonomic neuropathy. CONCLUSIONS: A large variability in QTc and QTd response was observed after hemodialysis. Autonomic neuropathy did not contribute to QTc and QTd length, nor to QTc and QTd change after dialysis.

Helicobacter pylori infection and gastric function in primary autonomic neuropathy.

Helicobacter pylori (Hp) infection in diabetic patients has been related to impaired gastric clearance of bacteria due to autonomic neuropathy. Gastrointestinal dysfunction has been described in primary autonomic failure (AF). The aim of the study was to evaluate, for the first time, the presence of Hp infection and gastric function in patients with primary AF Twelve patients with primary AF (aged 58-78), 31 healthy controls (aged 48-75) and 31 patients affected by type 2 diabetes (aged 46-75) were studied. A 13C-urea breath test was performed to assess the presence of Hp infection. To evaluate gastric function, AF patients underwent two non-invasive tests: 1) 13C-octanoic acid breath test (OBT) to evaluate gastric emptying, and 2) electrogastrogram (EGG) to evaluate gastric electrical activity. Hp infection was found in 100% of AF patients, in 48% of controls and in 71% of diabetic patients (p = 0.02 between groups). Electrical or mechanical gastric function was altered in 50% of AF patients. In particular, 1) after OBT, half-time gastric emptying was delayed in 6 out of 12 patients, and 2) EGG showed the presence of gastric dysrhythmias in 6 out of 12 patients. In conclusion, Hp infection was detected in all AF patients studied; as previously demonstrated in diabetes, such a finding might be related to autonomic neuropathy causing mechanical or electrical gastric dysfunction. Hp detection might be important for the gastrointestinal and extradigestive complications of such infection.