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The aim of the study was to evaluate the renin-angiotensin system and serotonin transporter gene polymorphisms in relation to hemodynamic parameters and heart rate variability during a head-up tilt test (HUT) in patients with vasovagal syncope.DNA was collected from 191 patients (mean age 44 ± 18 years, 61 men, 130 women). The following gene polymorphisms were determined in genomic DNA: angiotensin-converting enzyme insertion/deletion polymorphism (I/D ACE), angiotensinogen gene polymorphism (M 235), angiotensin II receptor type 1 (ATR1) polymorphism (A 11666C), and polymorphism of serotonin transporter gene (5HTTLPR). Heart rate variability during HUT was assessed in 5-minute intervals by low frequency, high frequency, standard deviation of the normal-to-normal (SDNN), and root mean square successive difference parameters.AA genotype of A 1166C polymorphism was associated with lower minimal systolic blood pressure (SBP) and diastolic blood pressure (DBP) during HUT compared with other genotypes (minimal SBP: AA 59.6 ± 21,8, AC 79.9 ± 22.7, CC 65.4 ± 22.7 mmHg, P = 0.007), (minimal DBP: AA 36.4 ± 22.7, AC 52.3 ± 22.9, CC 45.4 ± 19.5 mmHg, P = 0.007). AA genotype was also associated with higher SDNN compared to other genotypes in the early phase of HUT (SDNN in 5 minutes of tilt: AA 59.7 ± 24.6, AC 50.6 ± 20.6, CC 46.0 ± 13.2, P = 0.01) and at syncope occurrence (SDNN: AA 71.0 ± 20.9, AC 58.2 ± 17.9, CC 58 ± 10, P = 0.04)AA genotype of A 1166C polymorphism in the ATR1 gene may be associated with hypotension and decline in sympathetic tone during HUT. Its role in genetic predisposition to vasovagal syncope cannot be excluded.