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    Role of transforming growth factor-beta(2) in, and a possible transforming growth factor-beta(2) gene polymorphism as a marker of, renal dysfunction in essential hypertension: a study in Turkish patients
    (Elsevier Science Inc, 2005) Bicik, Zerrin; Gönen, Sevim; Bahçebaşı, Talat; Reis, Kadriye; Arınsoy, Turgay; Sindel, Şükrü
    Background: Many studies have shown that transforming growth factor (TGF)-beta has a major role in renal scarring in many renal diseases and hypertension. Objectives: The primary aim of this study was to investigate both the relationship between hypertension and serum and urinary levels of TGF-beta(2) (a more sensitive isoform for glomeruli than TGF-beta(1))), and the effects of combination therapy with perindopril + indapamide on microalbuminuria, which becomes an early indicator of hypertensive benign nephropathy, and serum and urinary TGF-beta(2) levels in patients with mild to moderate essential hypertension. In addition, we examined the possible relationship between TGF-beta(2) gene polymorphism and essential hypertension. Methods: This study was conducted at the Department of Nephrology, Medical Faculty, Gazi University, Ankara, Turkey. Patients aged >= 18 years with newly diagnosed mild to moderate essential hypertension (systolic/diastolic blood pressure [SBP/DBP] > 120/> 80 mm Hg) who had not previously received antihypertensive treatment were included in the study. Patients with stage I hypertension received perindopril 2 mg + indapamide 0.625 mg (tablet), and patients with stage 11 hypertension received perindopril 4 mg + indapamide 1.125 mg (tablet). All study drugs were given OD (morning) PO with food for 6 months. Serum and urinary TGF-beta(2) and creatinine levels and serum and urinary albumin levels were measured before and after perindopril + indapamide administration. Amplified DNA fragments of the TGF-beta(2) primer region were screened using amplification refractory mutation system polymerase chain reaction analysis, and the number of ACA repeats was confirmed by DNA sequencing. Genetic studies were performed using a commercial TGF-beta(2) kit. Results: Forty patients were enrolled in the study, and 38 patients (27 women, 11 men; mean [SD] age, 46.3 [6.5] years) completed it. SBP and DBP were significantly decreased from baseline with perindopril/indapamide (both, P < 0.001). Microalbuminuria and urinary TGF-beta(2) levels also decreased significantly from baseline (P = 0.04 and P < 0.001, respectively), whereas the serum TGF-beta(2) level did not change significantly. Three patients, all of whom were found to have TGF-beta(2) gene mutations, had increased urinary TGF-beta(2) levels despite good blood pressure control. Conclusions: The results of this study in patients with mild to moderate hypertension suggest that, despite good clinical control of blood pressure, the persistence of microalbuminuria and high urinary TGF-beta(2) levels might predict renal impairment. When treating these patients, genetic tendencies and possible polymorphisms on the TGF-beta(2) locus should be kept in mind.