Background. Recent studies have demonstrated possible association between vitamin D deficiency and atherogenic dyslipidemia. However, there are practically no results from Russian investigations in this field. Objective. To assess serum lipids in women carrying various vitamin D receptor (VDR) gene variants. Design and methods . The study included 697 women aged between 35 to 55 years (mean age 43,4 ± 0,3 years). Anthropometric data including height, waist circumference, body mass index were measured. Serum lipid profile, 25-hydroxyvitamin D (25(OH)D) level and four VDR gene polymorphisms BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and FokI (rs2228570) were evaluated. The results showed high prevalence of abdominal obesity, dyslipidemia, vitamin D insufficiency/deficiency in the study group and 2,6 increased risk of high-density lipoprotein (HDL) cholesterol reduction in women with vitamin D deficiency. There were no differences in serum 25(OH)D between VDR genotypes. GG (BB) genotype carriers of BsmI (rs1544410) demonstrated higher triglyceride levels than subjects with GA, AA (Bb, bb) genotypes. Women with TT (AA) и TG (Aa) genotypes of ApaI (rs7975232) had higher total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared to GG (aa) genotype carriers. Conclusions. The study revealed the associations between low vitamin D status and decreased HDL cholesterol as well as between BsmI (rs1544410) and ApaI (rs7975232) VDR genotypes and atherogenic dyslipidemia.

High risk of macrovascular complications in patients with type 2 diabetes mellitus (T2DM) is caused by insulin resistance and atherogenic dyslipidemia that may be genetically determined. The aim of this study was to assess the association of polymorphic genetic variants APOA5 (S19W/rs3135506), CETP (Taq1B/rs708272), PON1 (Q192R /rs662) and PPARG (Pro12Ala /rs1801282) with T2DM and macrovascular complications in patients with T2DM resident in Northwestern Russia. We examined 386 patients with T2DM and 199 healthy controls. Genotyping was performed by polymerase chain reaction followed by restriction analysis. The study revealed the protective role of allele 12Ala of PPARG gene against T2DM development (odds ratio [OR]=0.58; 95% confidence interval [CI] 0.39-0.85). B1B1 genotype of CETP was associated with increased risk of stroke in T2DM patients (OR=1.85; 95%CI1.07-3.21). RR genotype of PON1 was associated with increased risk of T2DM with stroke (OR=2.98; 95%CI1.01-8.84). According to study results Pro12Ala (rs1801282) variant of PPARG affected the risk of T2DM; polymorphic variants of CETP (Taq1B/rs708272) and PON1 (Q192R/rs662) contributed to the risk of macrovascular complications of T2DM.

Objective. To compare the efficiency of atorvastatin monotherapy and combined therapy (atorvastatin and fenofibrate) in type 2 diabetes mellitus (T2DM) depending on the genotype of S19W apolipoprotein A5 gene polymorphism (APOA5). Design and methods. Altogether 135 patients with T2DM were enrolled, 114 women and 21 men (mean age 59,3 ± 0,3 years) taking biguanides, with HbA1c < 8,0 %. None of them received lipid-lowering therapy. Clinical data, serum lipids and genetic variants of АPOА5 were assessed. Atorvastatin monotherapy (20 mg/day/3 months) was initially prescribed with subsequent change to the combination therapy by atorvastatin and fenofibrate (20 mg + 145 mg/day/3 months). Results. Three-month monotherapy led to a significant reduction in triglycerides (TG) and very low density lipoproteins cholesterol (VLDL-cholesterol) levels in patients with SS genotype compared to carriers of SW genotype (p = 0,015 and p = 0,025, respectively). At the same time, after 3‑month combination therapy no differences were found between АPOА5 variants. There was a trend towards greater reduction in total cholesterol, TG, and VLDL-cholesterol in SW-carriers compared to SS-carriers. There was a paradoxical decrease in high density lipoproteins cholesterol (HDL-cholesterol) in patients with SW genotype, while it remained unchanged in patients with SS genotype. Conclusions. Our results suggest that polymorphic variants in АPOА5 may affect pharmacogenetics of lipid-lowering therapy in T2DM.

Objective. To evaluate the association of polymorphic genetic variants PON1 (Q192R /rs662) and CETP (Taq1B/rs708272) with cardiovascular risk in T2DM patients resident in Saint-Petersburg, Russia. Design and methods. 386 patients with T2DM, 299 women and 87 men, mean age 59,3 ± 0,3 years, and 199 healthy controls were examined. Genotyping was performed by polymerase chain reaction followed by restriction analysis. Results. B1B1 genotype of CETP was associated with increased risk of stroke in T2DM patients (OR=1.85; 95% CI 1.07-3.21). RR genotype of PON1 was associated with increased risk of T2DM with stroke (OR=2,98; 95% CI 1,01-8,84). Conclusion. Polymorphic variants of CETP (Taq1B/rs708272) and PON1 (Q192R/rs662) contribute to the cardiovascular risk in T2DM.

Study objective: to estimate efficiency of atorvastatin therapy in patients with type 2 diabetes mellitus (T2DM), who are the carrier of various genotypes Q192R paraoxonase gene 1 (PON1). 386 T2DM patients, who have not received statin therapy before, and 187 healthy people were examined. All those examined were exposed to blood lipid profile testing and molecular genetic research. The atorvastatin treatment group included 164 T2DM patients with abnormality of lipids, their blood lipid profile values were assessed before and after 3 months of the therapy. Blood lipid profile values did not differ in type 2 diabetes mellitus patients (T2DM) - the carriers of different Q192R genotypes of paraoxonase gene 1 (PON1) polymorphism. Atorvastatin therapy decreased atherogenic lipoprotein levels in type 2 diabetes mellitus patients (T2DM) - the carriers of different Q192R genotypes of paraoxonase gene 1 (PON1) polymorphism, but reduction degree in the carriers of different Q192R genotypes differed - in Q192Q bearers it was greater than in the bearers of Q192R genotype of gene PON1 (р = 0,031). Atorvastatin 3-months therapy revealed greater reduction of total cholesterol in the carriers of Q192Q genotype of gene 1 (PON1) than in the carriers of Q192R genotype of gene 1 (PON1).

The article deals with genetic aspects of the influence of S19W polymorphic variants of apolipoprotein A5 gene, on the blood lipids in patients with type 2 diabetes mellitus, as well as influence of various clinical and anamnestic parameters on the blood lipids determining the development f atherogenic dyslipidemia.. The study revealed interrelation between 19W allele and hypertriglyceridemia development in patients with type 2 diabetes mellitus.

Objective. To determine whether cardiac autonomic neuropathy (CAN) influences the development of arterial hypertension (HTN) in patients with type 1 diabetes mellitus (T1DM). Design and methods. We examined 60 patients with T1DM (37 women and 23 men, mean age 40,3 ± 1,3 years) and 40 healthy controls (21 women and 19 men, mean age 30,0 ± 0,6 years). Clinical symptoms of CAN as well as instrumental parameters were assessed. The following methods were used: spectral analysis of heart rate variability, blood pressure changes during tilt-test, the Valsalva maneuver, test with deep respiration, hand-grip and cold-pressor test, an index 30/15, arterial and cardiopulmonary baroreflexes. Blood pressure monitor (Finometer) and occlusion plethysmograph (Dohn) with parallel registration of electrocardiogram were used for data assessment. Results. Clinical symptoms of CAN had 39 patients with T1DM (65%), in 30 of them CAN was confirmed by instrumental methods. In 9 patients without clinical manifestations CAN was diagnosed instrumentally. The most frequent disorders in T1DM patients were the reduction of spontaneous arterial baroreflex (69%), cardiopulmonary baroreflex (64%), and heart rate variability (49%). HTN was diagnosed in 37 T1DM patients (62%) and was more frequent in patients with autonomic dysfunction (р < 0,05).The patients with CAN had longer duration of HTN (5,7 ± 2,80 vs 2,3 ± 2,80 years, р < 0,05) and higher HTN degree (χ2 = 8,06, р < 0,01) than patients without CAN. Conclusions. Cardiac autonomic neuropathy contributes to the development of HTN in T1DM patients. Implementation of instrumental methods for timely diagnosis of CAN is reasonable in T1DM patients.

Особенности липидного обмена и сердечно-сосудистые заболевания у больных сахарным диабетом 2 типа, проживающих в Санкт-Петербурге, — носителей различных генотипов taqib полиморфизма гена белка, переносящего эфиры холестерина

Aim. To assess the specifics of lipid metabolism and efficacy of atorvastatin therapy in Saint-Petersburg citizens, having 2 type diabetes (DM2) — the carriers of various TaqIB gene polymorphisms, the cholesterol ethers transporting protein (CETP).Material and methods. Totally 382 patients studied, with DM2, native for statins, and 187 almost healthy individuals. All participants underwent blood sampling with lipids test and molecular-genetic testing. Into atorvastatin group we included 164 patients with DM2 and dyslipidemia. Lipid profile parameters were assessed at baseline and in 3 months of atorvastatin therapy.Results. In almost healthy individuals the carriage of B1B2 genotype of TaqIB polymorphism of CETP gene is associated with higher levels of triglycerides, low density lipoproteides cholesterol, very low density cholesterol and atherogenity coefficient, comparing to these values in B2B2 carriers. DM2 patients had higher triglycerides level if B1B1 comparing to B2B2. In DM2 type, triglycerides level also was higher in B1B1 than in B2B2 (p=0,044); other lipid spectrum parameters did not differ between two groups. While comparing the efficacy of atorvastatin therapy in various genotypes carriers of TaqIB polymorphism gene CETP, there were no differences of the studied parameters within treatment. While evaluating the target levels reach of lipid spectrum on the atrovastatin therapy it was found, that only B1B1 carriers reached target triglycerides level (p=0,017).Conclusion. In DM2 patients the arrangement of genotypes and alleles of TaqIB polymorphism of CETP gene did not differ of this in healthy individuals; in carriers of different genotypes of this gene lipidogram parameters at baseline and on treatment by atorvastatin for 3 months did not differ; in B1B1 carriers the levels of triglycerides reached target values on atorvastatin.

The article deals with the features of lipid metabolism in patients with type 2 diabetes - the carriers of different genotypes of paraoxonase 1 gene. Known that the enzyme paraoxonase 1 (PON1) plays a key role in the regulation of lipid peroxidation and its activity is genetically determined. The investigation revealed that the PON1 gene's polymorphic variants may determine the formation of atherogenic changes in lipid profile in patients with diabetes mellitus (DM) type 2.

Pathogenesis of hypertension in overweight and obese patients is to be studied due to the great theoretical and practical importance. The additional mechanisms directly involved in the development of hypertension in subjects with abdominal obesity have been determined. Functional disorders of adipose tissue were shown to play an important role in the development of hypertension in obese patients, and in some cases adiposopathy can be the primary cause of hypertension. Renin-angiotensin-aldosterone system was shown to change signifi cantly in obesity. Understanding the causes and mechanisms of hypertension in patients with abdominal obesity is of particular interest because it allows more focused prevention and treatment of the disease.

Peroxisome proliferator receptors alpha (PPAR-α) and their role in atherogenesis has a great practical significance, since there are drugs that can enhance the activity of these receptors. Activation of PPAR-α by fibrates is known to lead to both significant reduction of serum triglyceride levels by activation of lipoprotein lipase, and to the increase of synthesis of the main apolipoproteins within high-density lipoproteins (HDL), contributing to the reverse transport of cholesterol from chylomicrons and very low-density lipoproteins to the liver. Besides, PPAR-α increase the capture of HDL by liver. PPAR-α also participate in the regulation of inflammation, expression of adhesive molecules, production of chemotactic factors, as well as inhibit the proliferation of smooth muscle cells and activity of fibroblasts. These data suggest that PPAR-α are directly involved in the processes of atherogenesis, and their activation may contribute to the regression of atherosclerotic plaque and significant reduction of cardiometabolic risk.

Vessel occlusion by rupture or atheroma erosion leading to thrombosis is the underlying cause of severe complications, including sudden cardiac death, myocardial infarction, and stroke. Tissue factor is known to play the key role in the initiation of the majority of stages of coagulation cascade. Recent studies explained the structure, synthesis and activation mechanisms of tissue factor. Tissue factor is the main component of atherothrombotic process and is associated with the immune inflammation, endothelial dysfunction, angiogenesis, and cell migration that play an important role in the development of cardiovascular, inflammatory and oncological pathology. Basal activity of tissue factor is the independent parameter of cardiovascular risk, the predictor of thrombolysis efficacy and affects the results of angioplasty interventions. The effects of medications (e.g. statins), including those in drug-eluting stents, on tissue factor are the objective of further investigation. Studies of physiological and pathogenic role of tissue factor will have a great impact on our understanding of cardiovascular pathology and other diseases.

The metabolic cardiovascular syndrome (MS) is a common cluster of metabolic abnormalities (abdominal obesity, hypertension, dyslipidemia and carbohydrate metabolism disorders) that are related to insulin resistance and hyperinsulinemia and are associated with accelerated atherogenesis. Insulin excess is known to promote the development of the whole metabolic cascade. Recently it has been shown that the inflammatory and hemostatic abnormalities, immunological disorders, endothelial dysfunction, hyperhomocysteinemia and hyperuricemia are also important features of MS. Despite the numerous studies of MS its underlying cause is still not established. The dysfunction of visceral adipocytes (adiposopathy) might be genetically determined, and is considered nowadays as the main factor contributing to the development of the MS. Understanding the underlying mechanisms is of particular interest for prevention and target therapy of all the components of MS.

Arterial hypertension in patients with metabolic cardiovascular syndrome (MS) has a number of features which are of great theoretical and practical significance. It has been shown that hypertension is the most frequent component of MS and chronologically follows abdominal obesity while clinical manifestations of atherosclerosis and carbohydrate metabolism disturbances develop much later. In addition, the disorders of hypothalamic-pituitary-adrenal axis contribute to the development of arterial hypertension in patients with abdominal obesity. Besides the abnormalities of central regulatory mechanisms, increased sympathetic tone, insulin resistance and hyperinsulinemia, functional state of adipose tissue is an established important factor for the development of systemic hypertension in patients with abdominal obesity, and in some cases the dysfunction of adipocytes, which can be genetically determined or acquired, may cause the whole cascade of MS. Search for the causes and mechanisms of arterial hypertension in patients with MS can help to find the possible targeted treatment and prevention of the disease.