Association of polymorphisms in endothelin-1 and endothelin receptor a genes with vasovagal syncope.

The endothelin system may play a role in the pathogenesis of vasovagal syncope (VVS) because it is implicated in blood pressure regulation. We hypothesized that endothelin-related genetic polymorphisms might modulate susceptibility to VVS. This study aimed to evaluate the possible influence of endothelin-1 (EDN1) and endothelin receptor A (EDNRA) gene variants on the occurrence of tilt-induced VVS and autonomic nervous system activity during the head-up tilt test (HUT). Results were expressed as mean +/- SEM. In 254 patients with recurrent syncope (age 45.33+/-1.22 years, 94 males, 160 females), heart rate variability (HRV) was measured during HUT. EDN1 rs5370 G>T and EDNRA rs5333 T>C gene polymorphisms were assessed using high-resolution melting analysis. There was no statistically significant association between polymorphisms EDN1 rs5370 and EDNRA rs5333 and positivity of HUT or hemodynamic types of VVS. Patients with GT or TT genotypes at the rs5370 locus of the EDN1 had significantly higher values of high-frequency (HF) and the standard deviation of the average NN intervals at the time of the syncope, and they tended to have lower low-frequency (LF) and LF/HF ratio when compared to homozygotes (GG). No statistically significant differences were found in HRV parameters concerning the EDNRA rs5333 genotypes. Our findings suggest the potential role of EDN1 rs5370 variants in regulating autonomic nervous activity and pathogenesis of VVS.

Insulin-like growth factor (IGF) system and hormonal-metabolic profile in women with polycystic ovary syndrome.

AIM of the study was to compare serum levels of IGF-1, IGF-2 and insulin­like growth factor­binding protein 3 (IGFBP-3) among non­obese and obese PCOS women, and to assess their relationship to metabolic and hormonal parameters.    METHODS: The study included 64 women diagnosed with PCOS (age 28.9 ± 5 years); 30 of them with BMI > 27 and 34 with BMI lower than 27. All subjects were examined for parameters of glucose and lipid metabolism, steroid hormones and serum IGF-1, IGF-2 and IGFBP-3 levels. RESULTS: No significant differences in serum IGFBP-3 (p=0.534), IGF-1 (p=0.29) and IGF-2 (p=0.56) between two groups have been detected. IGFBP-3 was in positive correlation with total cholesterol (p=0.026), LDL cholesterol (p=0.03) and triacylglycerols (p=0.022). IGF-1 were negatively correlated with insulin (p=0.022), HOMA IR (p=0.033), triacylglycerols (p=0.0196) and waist circumference (p=0.049). A positive correlation was detected between IGF-1 and HDL cholesterol (p=0.025). No significant relationship was observed between IGF-1 and steroid hormones. CONCLUSION: Serum levels of IGF-1, IGF-2 and IGFBP-3 in obese PCOS women do not differ from those detected in non­obese PCOS women. IGF-1 negatively correlated with metabolic parameters, indicating that lower IGF-1 may represent an important predictor of metabolic syndrome (MS) in PCOS women. All peptides seem to have little effect on ovarian steroidogenesis in PCOS (Tab. 1, Fig. 1, Ref. 30).

Relationship between steroid hormones and metabolic profile in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is commonly associated with a higher cardiometabolic risk. The relationship between steroid hormones and cardiometabolic profile in PCOS has been evaluated, but no single hormonal predictor of this association has been identified to determine. To determine the relationship between steroid hormones and cardiometabolic risk factors in PCOS women. Study included 64 women diagnosed with PCOS. Fasting blood samples were analyzed for biochemical, metabolic parameters and sex steroid hormones. PCOS women with BMI>/-27 had significantly higher serum free testosterone (FT), free androgen index (FAI), estrone (E1) (p=0.014, p=0.02, p=0.01) than those with normal weight. In all subjects E1 positively correlated with BMI (p=0.0067), serum insulin (p=0.0046), HOMA-IR (p=0.0125) and negatively with HDL-cholesterol (p=0.009). FAI positively correlated with serum cholesterol (p=0.0457), triacylglycerols (TAG) (p=0.0001), HOMA-IR (p=0.037), and glycemia (p=0.0001), negatively with HDL-cholesterol (p=0.029). In multiple linear regression model E1 most significantly predicted HOMA-IR, whereas FT/FAI predicted HDL-cholesterol and BMI. We conclude that PCOS women with marked overweight or obesity have higher FT, FAI and E1 as compared with nonobese PCOS subjects. E1 and FT may predict worse cardiometabolic profile in PCOS.

Environmental estrogen bisphenol A and autoimmunity.

Over the past few years, there has been evidence of the increasing prevalence of autoimmune diseases. Autoimmune diseases consist of many complex disorders of unknown etiology resulting in immune responses to self-antigens. The immune system, and its function, is under complex and integrated control and its disruption can be triggered by multiple factors. Autoimmunity development is influenced by multiple factors and is thought to be a result of interactions between genetic and environmental factors. Here, we review the role of a specific environmental factor, bisphenol A (BPA), in the pathogenesis of autoimmune diseases. BPA belongs to the group of environmental estrogens that have been identified as risk factors involved in the development of autoimmune diseases.

[The environmental estrogen bisphenol A and its effects on the human organism]. / Environmentálny estrogén bisfenol A a jeho úcinky na organizmus cloveka.

Bisphenol A (BPA), i.e. an environmental estrogen, is one of the most common synthetic chemicals which enter the human body from plastic bottles, food packaging and dental materials. As many studies show, a longterm exposure to BPA is connected with a risk of developing various diseases and endocrine disorders. Exposure to BPA, particularly during development, increases the risk of breast carcinoma, obesity, diabetes mellitus type 2 as well as reproductive disorders. It also increases the risk of testes carcinoma and prostate carcinoma. Some isolated studies support also the relation between BPA and the risk of cardiovascular and autoimmune diseases. The effect of other xenoestrogens, such as polychlorinated biphenyls, phthalates, dioxins, as well as others, is similar or perhaps even stronger. For the time being, however, the exact pathophysiologic mechanisms of these relations are not quite clear and require further experimental, but especially human, studies.