INTERRELATION OF GENE POLYMORPHISM AND ENDOTHELIUM DYSFUNCTION IN UZBEK HYPERTENSIVE PATIENTS: PP.21.337
Annotatsiya
Background: Genetic elements contribute to 30–50% of the blood pressure variability. The underlying pathological defect in essential hypertension (EH) is due, at least in part, to endothelial dysfunction (ED). ED is recognized as an early stage in the pathogenesis of EH. Aim of the study was to evaluate the association of gene polymorphisms (ACE/ID, AGT/M235T, AT1R/A1166C, CYP11B2/C344T, BKRB2/ + 9–9, ecNOS/4a4b, GNB3/C825T, ARB2/Gln27Glu) with ED in Uzbek hypertensive men. Methods: The study included 174 nonsmoking men (46.8 ± 9.6 yr) with untreated EH of stage I-II. The total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) levels were determinated. Low-density lipoprotein cholesterol (LDL-C) level was calculated by the Friedewald formula. Microalbuminuria was defined as an albumin urinary excretion (AUE) level by immunoturbidimetric assay. Carotid intima-media thickness (IMT) was measured by high-resolution ultrasound. ED was evaluated by measuring of the flowmediated dilatation (FMD) of the brachial artery (BA) with a 7.5 MHz linear array transducer. Genomic DNA was extracted from peripheral blood. PCR-RFLP-based analysis of gene polymorphisms (GP) was performed. Statistical analysis was performed using a Microsoft Office Excel 2007 and Statistica v6.0. Results: Patients were divided into two groups: with δFMD>10% and δFMD < 10% for the determination of GP association with ED. Only the T-allele and MT-, TT-genotypes of the AGT gene were associated with an increased risk for ED: OR 3.18 (95% CI: 1.80–5.63); OR 2.24 (95% CI: 1.08–4.66); OR 15.94 (95% CI: 0.95–268.79). Multivariate logistic regression analysis (dependent variable: δFMD; independent variables: AGT genotype status, age, BMI, SBP, DBP, TC, HDL-C, IMT, AUE, atherogenity index, BA baseline diameter) confirmed the negative association between the MM genotype of the AGT gene, positive association between IMT and ED. We did not find a clear association of ED with other GP. Carriers of C-allele of AT1R gene, -9-allele of B2BKR gene and 4a-allele of ecNOS gene have more disorders of FMD. Conclusions: Only the TT genotype of AGT gene was significantly associated with the risk of ED.