Search

Aim: to study an association between T455C apolipoprotein C-III (apo C-III) gene polymorphism, insulin resistance (IR), metabolic syndrome (MS) and its components in a Kyrgyz ethnic group., Material and Methods: 259 persons: 162 patients with MS and 97 sex and age matched controls without MS, diabetes mellitus and cardiovascular diseases were included in the study. Clinical examination with arterial blood pressure, anthropometric data measurement and laboratory tests for blood glucose and lipid parameters were performed in all included persons. In 140 patients test for immunoreactive serum insulin was done. DNA was extracted from blood cells and T455C polymorphism of apo C-III gene was determined by PCR method., Results: In examined persons the most frequent was TC genotype as in group with MS as in controls. The difference on genotype's frequency between group was close to significant level (χ2 =5.48; p = 0.06) and odd ratio (OR) for MS between CC and TT carriers was 2.57 (95% CI 1.15-5.72); p = 0.019). Frequency of 455C allele in control group was--0.44 and in group with MS--0.54 (χ2 = 4.55; p = 0.036). In carriers of CC genotype there was noted that the frequency of IR (61.8% vs 23.1% vs 36.3%; p < 0.005), insulin level (11.9 [7.04-16.3] vs 5.73 [3.34-10.3] vs 7.54 [4.59-12.2] µIU/ml; p < 0.01) and HOMA index (3.14 [1.66-4.79] vs 1.46 [0.8-2.6] vs 2.05 [1.12-3.6]; p < 0.01) were significantly higher compared with TT and TC genotypes groups respectively. OR for IR between CC and TT carriers was 5.39 (95% CI 1.7-16.9; p = 0.0028). There also was an association between CC genotype and other MS components such as abdominal obesity (χ2--6.24; p--0.044, OR (95% CI--2.21 [1.03-4.82]) and high level of blood triglycerides (χ2--7.57; p--0.022, OR (95% CI) 2.5 [1.14-5.5])., Conclusion: In examined Kyrgyz ethnic population the most frequent was heterozygous TC genotype of T455C polymorphism of apo C-III. An association of 455C allele and CC genotype with MS, IR, abdominal obesity and high level of triglycerides was revealed. Key words: apolipoprotein C-III; T455C gene polymorphism; metabolic syndrome, insulin resistance.

There were examined 219 women of Kyrgyz nationality (mean age 51 ± 9.7 years). 117 female with breast cancer (BC) and 102 apparently health controls. The diagnosis of breast cancer was confirmed histologically. DNA was prepared from whole blood samples. XRCC1 genotypes Arg399Gln were examined using polymerase chain reaction-restriction enzyme polymorphism (PCR-RFLP). The frequency of the variant 399Gln allele and heterozygous genotype Arg399Gln of the Arg399Gln polymorphism of the XRCC1 gene were significantly higher among women with breast cancer compared with control subjects (p < 0.05). The Arg399Gln polymorphism of the XRCC1 gene is associated with breast cancer risk in a Kyrgyz women when using additive model (χ² = 4,901; p = 0.0268) general model (χ² = 13,86; p = 0.0010) and dominant model of inheritance (χ² = 11.18; p = 0.0008). Women having the 399Gln allele had 1,57 fold (95% CI 1.7-2.30; p = 0.002) higher risk of developing BC compared with subjects carrying neither of these alleles. Individuals carrying the heterozygous genotype Arg399Gln had 2.77 fold (95% CI 1.6-4, p = 0.002) higher risk of BC. Thus, the heterozygous genotype Arg399Gln and 399Gln allele of XRCClgene are associated with an increased risk of breast cancer in Kyrgyz females.

Goal: To study an association of G protein (GP) 3 subunit 825 polymorphism with obesity in native Kyrgyzes., Material and Methods: 210 persons: 89 patients (female - 35, male - 54) with obesity (body mass index [BMI] more or equal 30 kg/m2) and 121 apparently healthy controls (38 female, 83 male) with normal BMI. Arterial blood pressure, anthropometric measurement and laboratory tests for blood glucose and lipid parameters were performed in all examined persons. DNA was extracted from blood cells and GP3 subunit 825 polymorphism was determined by PCR method., Results: groups with TT and CT genotypes were combined together because of the rare frequency of TT genotype. Prevalence of + genotypes in group with obesity (0.72) was significantly higher than in controls - 0.52 (odds ratio 2.55, 95% confidence interval [CI] 1.31-4.23; =0.004). Arterial hypertension (45 vs. 31.3%; =0,049) and obesity (51.2 vs. 30%; p<0.01) occurred more often in + genotypes carriers compared with CC homozygotes. A logistic regression model for obesity showed significant effect of 825T allele (relative risk [RR] 2.89, 95% CI 1.25-6.7; =0.013) and irregular intake of vegetables (RR 3.47, 95% CI 1.52-7.94; =0.003) as predictors of obesity development independent of age, sex and physical activity level. In the regression model for arterial hypertension the 825T allele lost its significance after adjustment for obesity., Conclusion: GP3 subunit 825 allele in native Kyrgyzes is associated with obesity.

Aim: To study an association of C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) and insulin resistance (IR) among ethical Kirghizes., Methods: 132 Kirghiz patients with IR according to HOMA index (n=132) and sex and age matched patients without IR, diabetes mellitus (DM) type 2 or metabolic syndrome (MS) (n=132) were included into this study. Measurements of blood pressure (BP), body mass index, waist and hip circumference, fasting blood sugar, insulin, lipid parameters and C677T gene polymorphism of MTHFR were performed in all patients., Results: Frequency of CT and TT genotypes was significantly higher in patients with IR than in controls (2 - 7.22, p - 0,027, OR - 1.68, 95% confidence interval 1.13-2.5, p=0.027). T677 allele was also associated with obesity, hypertriglyceridemia and low level of high density lipoprotein cholesterol (HDL-C)., Conclusion: In Kirghizes carriage of T677 allele of MTHFR gene was associated with IR, abdominal obesity, hypertriglyceridemia and low HDL-C level.

For diagnostic assessment of the TB-biochip MDR test system, 455 sputum samples from new cases of pulmonary tuberculosis were tested. Unlike bacterial culture, the TB-biochip MDR test system allows identification of multidrug-resistant Mycobacterium tuberculosis (MBT) strains from mutations in the rpoB, katG, inhA, and ahpC genes rapidly during two days. Multidrug resistance of MBT to rifampicin and isoniazid was mainly due to the combined mutation Ser531 --> Leu in the rpoB gene and to the mutation Ser315 --> Thr in the katG gene.

A total 988 specimens were obtained from patients with pulmonary tuberculosis, which were all diagnosed according to clinical and X-ray and bacteriological studies. 940 patients were newly diagnosed without any history of treatment; 48 patients with a history of treatment one course. Mutations of rpoB, katG, inhA and ahpC gene associated with rifampicin (RIF) and isoniazid (INH) resistance were detected by "TB-Biochip" test system. Resistance was significantly higher in patients with a history of treatment compared with patients were newly diagnosed. Initial and acquired resistance were 53% (499/940) and 87% (41/48) respectively. Initial multidrug-resistance (MDR) (both to RIF and INH) was 30% (282/940) and acquired MDR was 75% (35/48). The single primary drug resistance only to RIF was 3% (29/940), to INH was 20% (188/940). The single acquired drug resistance only to RIF was 4% (2/48), to INH was 8% (4/48). The most common point mutations in rpoB gene were in codon 531 (58%), 526 (18%), 516 (9%) and 511 (6.8%). The point mutation Ser531-->Leu was at the highest frequency (59.7%). Resistance to INH was associated mostly with mutations found in katG gene-90.5%, inhA gene-9.05% and ahpC gene-0.45%. Prevalence of mutation was found in katG gene-Ser315 Thr (88.7%). The rifampicin and isoniasid resistance of M. Tb strains isolated in Kyrgyzstan is associated mostly with Ser531-->Leu mutation of rpoB gene, Ser315-->Thr mutation of katG gene. The "TB-Biochip" test system is simple and rapid for detection of rifampicin-and isoniazid resistant of M. Tuberculosis. The biochip-based analysis of RIF and INH susceptibility provides fast (less than 24 hours) and accurate identification of the mutations in gene rpoB, katG, inhA, ahpC responsible for resistance to rifampin and isoniazid.

The aim of this work was to evaluate the prevalence mutations in the rpoB, katG, inhA, ahpC gene of rifampicin and isoniazid resistant M. tuberculosis (Tb) isolates from Kyrgyz Republic using OA Biochip MDR. In the rifampicin-resistant strains, the mutations were identified in the codons 531, 526, 516, 511, 513, 512, 533, and 522. The most prevalent point mutations were Ser531RLeu at the codon 531 (59.7%). Resistance to INH was associated with mutations found in the katG gene (94.5%), inhA gene (3.5%), and ahpC gene (1.0%). The most prevalent mutations were SerRThr at the codon 315 (93.0%). The rifampicin and isoniasid resistance of the M. Tb strains isolated in Kyrgyzstan is associated mostly with Ser531RLeu mutation of the rpoB gene, Ser315RThr mutation of the katG gene, and InhT15 mutation.

The spectrum of drug-resistance of rifampicin-resistant M. tuberculosis strains to other first-line antituberculous drugs was studied. Streptomycin resistance was found to be prevalent in the structure of monoresistance. Resistance to two agents--isoniazid and streptomycin--was more common in the structure of polyresistance; that to a combination of isoniazid, rifampicin, and streptomycin was seen in the structure of multidrug resistance. The rifampicin-resistant strains were also resistance to isoniazid and streptomycin in 95.1 and 98.7% of cases, respectively. Resistance to isoniazid, streptomycin, and ethambutol occurs more frequently when cytosine is substituted for thymidine (TCG-->TTG) in codon 513 of the rpoB gene.

Two hundred and seventy-eight M. tuberculosis DNA samples taken from patients with clinically confirmed pulmonary and extrapulmonary tuberculosis were studied. Mutations of the rpoB, inhA, katG, and ahpC genes were analyzed by using multiple drug-resistant (MDR) biochips. A hundred and twenty-nine (46%) rifampicin- and isoniazid-sensitive strains and 149 (54%) resistant ones were detected. Out of the 149 drug-resistant strains, resistance to one drug (rifampicin or isoniazid) was revealed in 7 (4.7%) and 48 (32.3%) cases, respectively. The strains simultaneously resistant to both drugs were detected in 94 (63%) cases. In the Republic of Kyrghyzstan, patients with drug-resistant pulmonary tuberculosis were observed to have more commonly multidrug-resistant strains (63%) than the strains resistant to one drug (rifampicin or isoniazid). In this republic, the main cause of rifampicin resistance of Mycobacterium tuberculosis is the Ser531-Leu mutation of the rpoB gene in codon 531 and the Ser315-->Thr of the katG gene in codon 315.

Mapping modeling of the distribution of rifampicin-resistant tuberculosis was made in different regions of the Kyrghyz Republic. The results of determination of rifampicin resistance in Mycobacterium tuberculosis (MBT) by the biochip test were used to examine 904 MBT DNA samples taken when examining the patients living in different regions of the Kyrghyz Republic: Bishkek (n = 323), the Chui (n = 185), Issyk-Kul (n = 68), Naryn (n = 75), Talas (n = 47), Osh (n = 65), Dzhalal-Abad (n = 90), and Batken (n = 51) Regions. Comparison of the distribution of drug-resistant forms of tuberculosis by different regions revealed that rifampicin-resistant MBT strains were more frequently encountered in the densely populated regions of the republic - Bishkek and the Chui Region. Rifampicin resistance in MBT was caused by mutations in codons 531, 526, 522, 516, 511, 513, 512, and 513 of the rpoB gene. At the same time, there was a predominant selection of MBT with mutations in codons 531, 526, 516, and 511 in the republic. The spectrum of mutant MBT strains occurring in some regions varied. The broadest spectrum of genetic variability was observed in Bishkek and the Chui Region. Thus, Bishkek and the Chui Region are the hot points of concentration of mutant rifampicin-resistant MBT strains.

The present-day problems in tuberculosis control are associated with a difficulty in detecting Mycobacterium tuberculosis (MBT) in due time and in determining its drug sensitivity by conventional microbiological assays. The determination of the drug sensitivity of MBT takes much time from 2 weeks to 3 months, which fails to initiate and perform specific therapy timely. Molecular genetic techniques, including biochip analysis, yield results in 24-48 hours, which solves the problem of choosing and initiating adequate antibacterial therapy in the shortest possible time after tuberculosis is diagnosed. To assess the situation associated with the prevalence of rifampicin-resistant tuberculosis, by using the biochip analysis, the authors have examined 501 patients with tuberculosis who live in the Kyrghyz Republic. Drug resistance has been found in 40.3% of the examinees. At the same time, their primary and secondary drug resistance is 25.7 and 61.8%, respectively. In tuberculosis patients living in Kyrghyzstan, rifampicin resistance of MBT is more frequently due to mutations in 531 (59.2%), 526 (20.8%), and 516 (8.0%) codons in the rpoB gene.

Pulmonary hemodynamics, homeostasis and red blood parameters were studied in 77 rabbits in the mountains of the Tien Shan (3200 m above sea-level). Exposure of animals in alpine environment gave rise to pulmonary hypertension, polycythemia, alterations of homeostasis by the pattern of hyper- and hypocoagulation syndrome. On certain stages of adaptation products of paracoagulation were observed in blood as well as intravascular aggregation of formed elements, increased sensitivity of blood plates to platelet activation, increased fibrinolysis. Given existing hypothesis about involvement of changes in homeostasis and red blood in the pathogenesis of altitude pulmonary hypertension, the coefficients of paired linear correlation between indices of pulmonary hemodynamics and blood have been calculated. These coefficients are valid only for low values of the ratio.

In lowland (760 m above sea level) and highland (3200 m above sea level) of Tien Shan, the measurements of blood pressure and blood flow in the large vessels as well as the mass of heart ventricles of 75 rabbits have been made. In highland, the significant changes in hemodynamics of pulmonary circulation, appeared as elevations of pulmonary arterial pressure, pressure of wedging pulmonary artery, total and arterial pulmonary vascular resistance, have been noted. Besides this, adaptation to a highland staying was associated with an increased mass of the right ventricle of the heart. The pulmonary hypertension and hypertrophy of the right ventricle incremented during the first 2 weeks of the rabbits staying in highland and stabilized at achieved high level within succeeding 1.5 months of a tested period of adaptation. Because cardiac output and cardiac index starting from the end of 2nd week of adaptation did not differ significantly from control values, it can be said with confidence that an increase of pulmonary pressure in highland is dependent on a rise of pulmonary vascular resistance. In this case, the arterial pulmonary vascular resistance elevated to a greater extent than venous one. In highland, there revealed only the mean value of correlation relationship between the level of pulmonary blood pressure and a severity of right ventricle hypertrophy. The mass of left ventricle, systemic arterial pressure and total peripheral resistance did not significantly altered in a highland environment.