Khripun Irina 1, Vorobyev Sergey 1, Kogan Michael 1, Zitzmann Michael 2 1: Rostov State Medical University, Russia; 2: University Clinics, Centre for Reproductive Medicine and Andrology (CeRA), Germany No conflict of interests to declare Polymorphism in the androgen receptor gene and function of endothelium in men with type 2 diabetes. Recently, testosterone (T) deficiency has been described as an independent risk factor for cardiovascular morbidity and mortality. In addition, one of the mechanisms involved may be the CAG repeat (CAGn) polymorphism of the androgen receptor (AR) gene, conditioning the sensitivity to testosterone. However available data about the putative role of this polymorphism in the formation of endothelial dysfunction in men with type 2 diabetes mellitus (T2DM) are very limited. The aim of this study was to evaluate the impact of the CAGn polymorphism in the AR gene on biochemical and ultrasound markers of endothelial dysfunction in men with T2DM. We examined 92 men aged years with T2DM and determined the number of CAGn, total T, biochemical markers of endothelial dysfunction, namely ICAM-1, VCAM-1, p-selectin, e-selectin, resistin. Flow-mediated dilatation of the brachial artery (FMD-BA) was assessed. To estimate the linear dependence of variables we used ANOVA and regression models. Our study shows a significant positive association (R 2 = 0,687, p = 0,05) of total T levels with the number of CAGn in patients with T2DM. This pattern can be explained by a compensatory increase in the production of T for overcoming reduced sensitivity to androgens by increasing the length of CAGn. Longer CAGn were associated with increased concentrations of markers of endothelial damage: the number CAGn was significantly correlated with the levels of p-selectin (R 2 = 13,08; p = 0.049) and resistin (R 2 = 0,23; p = 0.032), reflecting a possible decrease in the sensitivity of the androgen receptor to the action of T. We also describe a novel ultrasound parameter of endothelial dysfunction - the time until the maximum FMD-BA is reached; endothelium-dependent reactivity seems to be mitigated not only in strength but also in rapidity in patients with longer CAGn (R 2 = 5,95, p = 0.04). A higher number of CAGn in the AR gene leads to endothelial impairment via the attenuation of sensitivity to androgens. For the first time in a diabetic population were found statistically significant relationships of the length AR gene CAGn and the time until the maximum vasodilatation of BA, which shows the slowing of endothelium- dependent vasodilation. Thus, a longer number of CAGn in the AR gene could be regarded as predictor of the development and progression of cardiovascular disease in men with T2DM. Acknowlegments This work was supported by the Russian Science Foundation, grant № INTRODUCTION MATERIALS AND METHODS RESULTS CONCLUSION Figure 1. Distribution of frequencies of CAGn in the AR gene among the studied patients. Figure 4. Diagram of the regression of the time until the maximum FMD-BA according to the number of CAGn in the AR gene Figure 2. Diagram of the regression of the resistin concentration according to the number of CAGn in the AR gene Figure 3. Diagram of the regression of the p-selectin concentration according to the number of CAGn in the AR gene ParametersR2R2 p Total cholesterol-0,1250,026 LDL-0,1020,039 Index of atherogenity-0,0470,01 Total Testosterone0,6870,05 P-selectin13,0770,05 Resistin0,2030,032 Time until the maximum FMD-BA5,9520,04 Baseline diameter of BA-0,490,024 Table 1. Logarithmic regression of biochemical and instrumental parameters, depending on the length of the CAGn in the AR gene. Table 2. Results of instrumental and biochemical assessment of endothelial function ParameterValue Test with reactive hyperemia Baseline diameter of BA, mm5,1 ± 1,0 Maximal diameter of BA during vasodilation, mm7,3 ± 0,3 Endothelial dependent vasodilation (EDVD), %12,33 ± 4,2 Patients with normal EDVD, %45,6 (n=42) Patients with abnormal EDVD, %54,4 (n=50) Biochemical markers of endothelial dysfunction ICAM-1,ng/ml422,3 ± 153,8 VCAM-1, ng/ml936,8 ± 362,2 Resistin, ng/ml5,6 ± 1,9 P-selectin, ng/ml752,2 ± 155,4 E-selectin, ng/ml53,2 ± 26,7 SAT Resistin, ng/ml Standardized predicted values by the number of CAGn in the AR gene P-selectin, ng/ml Time until the maximum FMD-BA, seconds Number of patients Number of CAGn