Hemodynamic parameters and heart rate variability during a tilt test in relation to gene polymorphism of renin-angiotensin and serotonin system.

PURPOSE: 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.

METHODS: 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.

RESULTS: 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)

CONCLUSION: 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.