International Journal of Biomedicine (Sep 2015)
Alpha-Adducin Gly460Trp Polymorphism and Clinical Efficacy of Indapamide in Uzbek Hypertensive Patients
Abstract
The purpose of the present study was to evaluate pharmacogenetic aspects of the antihypertensive, cardioprotective and vasoprotective efficacy of Indapamide in association with the ADD1 Gly460Trp polymorphism in Uzbek hypertensive patients. Materials and Methods: The study included 37 ethnic Uzbek patients (mean age of 47.14±9.54) with untreated hypertension (HT) of Grade 1 and 2 (ESH/ESC, 2013) and average HT duration of 5.7±4.33 years. All patients underwent clinical examination, echocardiography, Doppler sonography study, assessment of flow-mediated dilation (FMD) of the brachial artery and microalbuminuria (MAU) in daily urine. Genomic DNA was extracted from peripheral blood using the DiatomTM DNA Prep 200 Kit according to the manufacturer's protocol. The PCR-RFLP technique with visualization was performed to determine the ADD1 Gly460Trp polymorphism. Indapamide was prescribed as monotherapy for 12 weeks with an initial dose of 2.5 mg. Results: A 12-week monotherapy with Indapamide in a daily dose of 2.5mg showed the high antihypertensive efficacy of this drug expressing a reliable decrease in absolute values of SBP and DBP independently as carrying of the ADD1 Gly460Trp polymorphism allele. Positive changes in LVM during therapy in patients of both allele groups were accompanied by an improvement in LV diastolic function with significant positive dynamics of IRP. The target normalization of FMD was achieved only in the presence of Gly-allele, as well as a significant decrease in IMT and MAU during treatment. Conclusion: The results of our study showed high antihypertensive and cardioprotective efficacy of Indapamide treatment independently on carrying of the ADD1 Gly460Trp polymorphism. At the same time, we revealed certain advantages in the vasoprotective efficacy of Indapamide treatment in Uzbek hypertensive patients who are carriers of Gly-allele of the ADD1 Gly460Trp polymorphism.