GTP cyclohydrolase I gene polymorphisms are associated with endothelial dysfunction and oxidative stress in patients with type 2 diabetes mellitus.

BACKGROUND: The genetic background of atherosclerosis in type 2 diabetes mellitus (T2DM) is complex and poorly understood. Studying genetic components of intermediate phenotypes, such as endothelial dysfunction and oxidative stress, may aid in identifying novel genetic components for atherosclerosis in diabetic patients. METHODS: Five polymorphisms forming two haplotype blocks within the GTP cyclohydrolase 1 gene, encoding a rate limiting enzyme in tetrahydrobiopterin synthesis, were studied in the context of flow and nitroglycerin mediated dilation (FMD and NMD), intima-media thickness (IMT), and plasma concentrations of von Willebrand factor (vWF) and malondialdehyde (MDA). RESULTS: Rs841 was associated with FMD (p = 0.01), while polymorphisms Rs10483639, Rs841, Rs3783641 (which form a single haplotype) were associated with both MDA (p = 0.012, p = 0.0015 and p = 0.003, respectively) and vWF concentrations (p = 0.016, p = 0.03 and p = 0.045, respectively). In addition, polymorphism Rs8007267 was also associated with MDA (p = 0.006). Haplotype analysis confirmed the association of both haplotypes with studied variables. CONCLUSIONS: Genetic variation of the GCH1 gene is associated with endothelial dysfunction and oxidative stress in T2DM patients.

Endothelial function assessment in atherosclerosis: comparison of brachial artery flow­mediated vasodilation and peripheral arterial tonometry.

INTRODUCTION:  Endothelial dysfunction, characterized by the loss of nitric oxide bioavailability, is a key element in the pathogenesis of atherosclerosis and an important prognostic factor in cardiovascular diseases. Therefore, the development of reliable, safe, and noninvasive methods of endothelial function assessment is important for their use in cardiovascular risk stratification. Brachial artery flow­mediated dilation (FMD) is widely used in research but technical difficulties and problems with calibration between laboratories limit its clinical use. Reactive hyperemia-peripheral artery tonometry (RH­PAT, EndoPAT) has been developed as a simpler, cheaper, and potentially more reproducible method. OBJECTIVES:  We aimed to investigate associations between RH­PAT and FMD in relation to atherosclerotic risk factor profile. PATIENTS AND METHODS:  The study involved 80 subjects (52 men, 28 women) aged 43.6 ±14.8 years, with moderate­to­low cardiovascular risk (mean SCORE, 2.2% ±2%), in whom FMD, RH­PAT, and intima-media thickness (IMT) were determined. RESULTS:  The reactive hyperemia index (RHI) measured by RH­PAT correlated with FMD (r = 0.35, P <0.01). However, no significant correlation was observed between RHI and IMT, SCORE, or the number of classical atherosclerotic risk factors (hypertension, smoking, diabetes, hypercholesterolemia), while FMD was significantly correlated with IMT (r = -0.53, P <0.001), risk factors (r = -0.55, P <0.05), and SCORE (r = -0.4, P <0.05). CONCLUSIONS:  Despite its technical requirements, FMD is a more sensitive method than RH­PAT in evaluating the effect of classical atherosclerotic risk factors on vascular endothelial function. Microvasculature response during RH­PAT needs to be further studied, including the assessment of nonendothelial factors that may affect the measurements, before RH­PAT becomes the universal tool for the evaluation of the endothelial cells.

[Influence of tobacco dust on the respiratory system and selected immunological parameters]. / Wplyw pylu tytoniowego na uklad oddechowy i wybrane parametry immunologiczne.

UNLABELLED: Tobacco dust contains various immunologically active as well as toxic substances. However the relationship between allergic reactivity or lung function with chronic exposure to tobacco dust remains unclear. Accordingly the aim of the present study was to investigate the relationship between occupational chronic exposition to tobacco dust, respiratory function and some allergic reaction parameters. METHODS: 40 tobacco factory workers (47.5% women and 52.5% men) aged 25-59 years (mean 36.5) chronically (5-31 years, mean 12.6) exposed to tobacco dust were included into the study. Control group consisted of 30 subjects (46.7% women, 53.3% men) aged 25-60 years (mean 36.6) not exposed to tobacco leaves' dust. Detailed epidemiological data was collected. Additionally total IgE, specific (tobacco) IgE, eosinophil blood counts, skin tests (mixed grass and weed pollens, house dust, feather, tobacco extracts), basophil degranulation and neutrophil destruction tests with tobacco extracts as well as spirometry were studied in these groups. We found that FEV1/VC was significantly lower in tobacco industry workers chronically exposed to tobacco dust than in the control group (91.5 +/- 11.6% vs. 101.7 +/- 10.7% n; p = 0.0004). These subjects were also characterized by higher occurrence of mild bronchial obturation (FEV1/VC < 88% and FEV1 > 70%) which was present in 30% tobacco factory workers and in 6.7% of control group (p = 0.035). Levels of total IgE and tobacco-specific IgE, eosinophil counts, skin test reactivity, basophil degranulation and neutrophil destruction tests were not different between groups. CONCLUSIONS: Occupational chronic exposition to the dust of tobacco leaves is associated with significant increase in the occurrence of mild obturative ventilatory disturbances. Simultaneously no increased frequency of allergization to tobacco or other allergens was observed in tobacco industry workers.