The Protective Effect of Polymorphisms rs2681472 and rs17249754 of the ATP2B1 Gene Against Coronary Artery Disease and Hypertension is Abolished by Tobacco Smoking.

Aim    To study the relationship of single nucleotide polymorphisms rs2681472 and rs17249754 in the ATP2B1 gene with risk of ischemic heart disease (IHD) and arterial hypertension (AH) among residents of Central Russia and to evaluate the trigger role of smoking as a risk factor for development of IHD and AH in carriers of ATP2B1 gene polymorphic variants.Material and methods    The study included DNA samples from 1960 residents of Central Russia of Slavic origin. Among them, there were 1261 patients with cardiovascular diseases and 699 healthy persons. The vast majority of patients had both IHD and AH. Genotyping was performed using the iPLEX technique on a MassARRAY-4 genomic mass-spectrometer. The relationship of ATP2B1 alleles, genotypes, and haplotypes with the risk of diseases was calculated by logistic regression analysis with adjustments for sex and age.Results    Carriage of AG and GG (rs2681472) genotypes and GA (rs17249754) genotype was associated with a reduced risk of both IHD (p=0.0057 and p=0.022 for rs2681472 and rs17249754, respectively) and AH (p=0.016 and p=0.036, respectively). Rare rs2681472G-rs17249754G and rs2681472A-rs17249754A haplotypes were associated with a reduced risk of IHD (odds ratio, OR, 0.22; 95 % CI: 0.11-0.46, p=0.0001) and AH (OR, 0.22; 95 % CI: 0.10-0.47, p=0.0001). Analysis of the groups stratified by the smoking status showed that in smokers, the studied polymorphic variants did not have a protective action with respect of either IHD or AH. However, in non-smokers, the genotypes AG and GG rs2681472 (OR, 0.62; 95 % CI: 0.47-0.80, p=0.0004) and GA rs17249754 (OR, 0.61; 95 % CI: 0.47-0.81, p=0.0004) were associated with a reduced risk of IHD and AH (OR, 0.63; 95 % CI: 0.48-0.83, p=0.0004 for rs2681472; OR, 0.63; 95 % CI: 0.48-0.83, p=0.001 for rs17249754), as well as the carriage of the minor alleles rs2681472­G and rs17249754­A.Conclusion    It was shown for the first time that the polymorphic variants rs17249754 and rs2681472 of the ATP2B1 gene are associated with a reduced risk for IHD and AH only in non-smokers.

[Epidemiological and clinical aspects of chronic neuroborreliosis with parkinsonism in the Yaroslavl region]. / Epidemiologicheskie i klinicheskie aspekty khronicheskogo neiroborrelioza s sindromom parkinsonizma v Yaroslavskoi oblasti.

OBJECTIVE: To study clinical and epidemiological features of chronic neuroborreliosis (CB) with parkinsonism (PS) in the Yaroslavl region. MATERIALS AND METHODS: The study included the main group of patients (n=5) with CB and PS of the average age of 61±3/4, the comparison group (n=6) with Parkinson's disease (PD) of the average age of 54.7±8.3 and a group of 6 healthy people. Diagnostic criteria of Lyme disease based on the recommendation of the US Centers for Disease Control and Prevention and criteria for the diagnosis of PS were used. PD was diagnosed by the criteria of the Parkinson's UK Brain Bank. Serological diagnosis of CB was carried out using immunoenzyme assay and immunoblotting in dynamics. The following scales were administered: HOEHN and YAHR, MMSE, MFI-20, CGI. All patients underwent MRI of the brain and spinal cord. RESULTS AND CONCLUSION: PS in patients with CB in the Yaroslavl region was observed in 2.17% of cases among patients with CB and amounted to 0.25% of all cases of the revealed PS. The features that complicate the diagnosis of PS within chronic borreliosis were: the absence of erythema migrans in the history of 80% of patients and in more than half of the cases of the acute period of the disease, the presence in most patients (60%) of asymmetric onset of the PS with rest tremor in 40% cases and a significant reduction in the severity of PS as a result of therapy with levodopa. The onset of complete regression of the clinical manifestations of PS and reduction of the titer of antibodies and obtaining the negative results during dynamic serological study in response to prolonged antibiotic therapy provided a basis to verify the diagnosis of borreliosis with PS in these patients.

[Clinical, neuropsychological and epidemiological aspects of the 'transitional' form of Parkinson's disease in the Yaroslavl region]. / Kliniko-neiropsikhologicheskie i épidemiologicheskie aspekty 'perekhodnoi' formy bolezni Parkinsona v Iaroslavskoi oblasti.

AIM: To study clinical, diagnostic and epidemiological aspects of the 'transitional form' of Parkinson's disease (PD) in the Yaroslavl region. MATERIAL AND METHODS: The study included the main group of patients (n=11) with a 'transitional' form of PD, comparison groups (15 patients with essential tremor (ET), 15 patients with PD) and healthy individuals (n=15). Diagnostic criteria of MDS ET were used. PD was diagnosed by criteria of The Parkinson's UK Brain Bank. The following scales were administered: UPDRS, HOEHN and YAHR, MMSE), PDQ-39, EUROQOL part 2, STAI, HDRS. RESULTS AND CONCLUSION: The period of 15.7±5.8 years, characterized by bilateral postural-kinetic tremor, preceded the appearance of signs of parkinsonism in the 'transitional' form of PD. This form of PD was characterized by slow progression, lack of cognitive and depressive disorders and less severity of anxiety disorders. In most cases, there was a head tremor (63.6%), a positive family history of ET in two generations (100%), the onset of parkinsonism from the left extremities (81.8%). The frequency of hyposmia was comparable to patients with PD. Quality of life indicators were significantly higher compared to PD patients. A genetic predisposition, which subsequently affects the development of parkinsonism, probably, underlies a rare phenotype associated with the transformation of ET into PDis.

[ESTIMATING THE EFFECTIVENESS OF HYPOLIPIDEMIC THERAPY WITH ROSUVASTATIN IN PATIENTS WITH CORONARY HEART DISEASE DEPENDING ON THE GENOTYPE OF LIPOPROTEIN LIPASE].

Taking into account the genetic heterogeneity of hyperlipidemias, polymorphic genes involved in the regulation of lipid metabolism may explain differences in the efficacy of hypolipidemic therapy. In the present prospective and randomized study, we have investigated the efficacy of rosuvastatin (10 mg/day) in the therapy of atherogenic hyperlipidemias in a group of 62 patients with coronary heart disease (CHD), depending on the genotype of lipoprotein lipase (LPL). The pharmacological correction was carried out during one year under control of lipid metabolism parameters (total cholesterol, LDL-C, HDL-C, HDL-unrelated cholesterol, triglycerides, atherogenic index) at the baseline and on 4th, 8th, 24th and 48th week. The HindIII polymorphism (+495T > G, rs320) of the LPL gene was genotyped in all patients studied through a real-time PCR TaqMan assay. Rosuvastatin produced a significant hypolipidemic effect with respect to all investigated lipid metabolism parameters for 24 weeks of treatment. Changes in the parameters of lipid metabolism upon rosuvastatin treatment differed in patients with genotype +495GG as compared to the rest LPL genotypes. In comparison to the +495TT and TG genotypes, the genotype +495GG showed a greater reduction in total cholesterol on 8th week, and in LDL-C, HDL-unrelated cholesterol, and atherogenic index on the 48th week of rosuvastatin therapy (p <0.01). It can be suggested that the pronounced hypolipidemic effect of rosuvastatin in homozygotes +495GG of the LPL gene is associated with modulation of the LPL activity, as it has been previously reported for other statin drugs.