Исследования и публикации

Association Between 28 Single Nucleotide Polymorphisms And Type 2 Diabetesmellitus In The Kazakh Population: Acase-Control Study

Background: We evaluated the associations between single nucleotide polymorphisms and different clinical parameters related to type 2 diabetes mellitus (T2DM), obesity risk, and metabolic syndrome (MS) in a Kazakh cohort. Methods: A total of 1336 subjects, including 408 T2DM patients and 928 control subjects, were recruited from an outpatient clinic and genotyped for 32 polymorphisms previously associated with T2DM and obesity-related phenotypes in other ethnic groups. For association studies, the chi-squared test or Fisher’s exact test for binomial variables were used. Logistic regression was conducted to explore associations between the studied SNPs and the risk of developing T2DM, obesity, and MS, after adjustments for age and sex. Results: After excluding four SNPs due to Hardy-Weinberg disequilibrium, significant associations in age-matched cohorts were found betweenT2DM and the following SNPs: rs9939609 (FTO), rs13266634 (SLC30A8), rs7961581 (TSPAN8/LGR5), and rs1799883 (FABP2). In addition, examination of general unmatched T2DM and control cohorts revealed significant associations between T2DM and SNPsrs1799883 (FABP2) and rs9939609 (FTO). Furthermore, polymorphisms in the FTO gene were associated with increased obesity risk, whereas polymorphisms in the FTO and FABP2 genes were also associated with the risk of developing MS in general unmatched cohorts. Conclusion: We confirmed associations between polymorphisms within the SLC30A8, TSPAN8/LGR5, FABP2, and FTO genes and susceptibility to T2DM in a Kazakh cohort, and revealed significant associations with anthropometric and metabolic traits. In particular, FTO and FABP2 gene polymorphisms were significantly associated with susceptibility to MS and obesity in this cohort.

Keywords: Genetic variants, Kazakh cohort, Metabolic syndrome, Obesity, Type 2 diabetes mellitus

Молекулярно-генетические особенности болезни паркинсона

Болезнь Паркинсона (БП) является хронической неуклонно прогрессирующей болезнью, которая встречается во всех популяциях мира. Развитие симптомов как ригидность мускулатуры, тремор, брадикинезия, нарушение позы, коррелирует с гибелью дофаминергических нейронов черной субстанции мозга (ЧС), связано со снижением концентрации дофамина в полосатом теле мозга. Механизм гибели дофаминергических нейронов ЧС при БП остаётся неясным. Несмотря на имеющиеся данные о выявленных генах и локусах, участвующих в развитии БП, молекулярные механизмы возникновения и прогрессирования этого заболевания до конца не изучены.

Polymorphisms In Genes Involved In The Absorption, Distribution, Metabolism, And Excretion Of Drugs In The Kazakhs Of Kazakhstan

Studies of genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are crucial to the development of therapeutics in clinical medicine. Such data provide information that may improve our understanding of individual differences in sensitivity or resistance to certain drugs, thereby helping to avoid adverse drug reactions (ADRs) in patients and improve the quality of therapies. Here, we aimed to analyse single nucleotide polymorphisms (SNPs) involved in the ADME of multiple drugs in Kazakhs from Kazakhstan. These results provide further information for pharmacogenetic databases and may contribute to the development of personalized approaches and safer therapies for the Kazakh population. Moreover, these data provide insights into the different racial groups that may have contributed to the Kazakh population.

Keywords: Kazakhstan, Single nucleotide polymorphism, Adsorption, Distribution, Metabolism, Excretion, OpenArray.

Genetic Risk Factors For Restenosis After Percutaneous Coronary Intervention In Kazakh Population

After coronary stenting, the risk of developing restenosis is from 20 to 35 %. The aim of the present study is to investigate the association of genetic variation in candidate genes in patients diagnosed with restenosis in the Kazakh population. Our results indicate that FGB (rs1800790), CD14 (rs2569190), and NOS3 (rs1799983) SNPs could be genetic markers for development of restenosis in Kazakh population. Adjustment for potential confounder factor BMI gave almost the same results.

Keywords: Coronary heart disease, Restenosis, SNP, Genotyping

Antibiotic Resistance Of Helicobacter Pylori Isolates From Kazakh Patients

Helicobacter pylori strains can be resistance to important triple combination therapies for H. pylori eradication. The aim of the study was to investigate the rate of resistance to clarithromycin, metronidazole, amoxicillin, tetracycline, rifampicin, and to detect antibiotics resistance associated mutations in H. pylori isolates from patients in Kazakhstan. Susceptibility of 20 H. pylori strains was tested by E test method. The genes of resistant and susceptible clinical isolates were sequenced in order to assess resistance and non-resistance associated genetic alterations. From 20 clinical isolates examined 8(40%) showed phenotypic resistance to metronidazole (MIC >256 mg/L), 13(65%) to clarithromycin (MIC >256 mg/L), and 1(5%) to amoxicillin (MIC >6 mg/L). The majority of resistance strains had point mutations in the 23S rRNA gene, in rdxA gene, and one strain in pbp1A gene. The rest of isolates with moderate resistance isolates (MIC <0.016 mg/L) showed a drug-susceptible phenotype and did not harbor any mutation in the sequence of the genes. In Kazakh population of existing clarithromycin and metronidazole resistance, three tetracycline, amoxicillin and rifampicin could be helpful in rescue regimens with unsuccessful H. pylori eradication.

Keywords: Helicobacter pylori, clarithromycin, metronidazole, amoxicillin, tetracycline, rifampicin