ObjectivesAssessment of the significance of online queries regarding smell impairment to evaluate the epidemiological status and effectiveness of COVID-19 epidemic control measures using levofloxacin ...as an example.SettingThere are 81 regions of Russia and several large cities, such as Moscow, St. Petersburg and Nizhny Novgorod.MethodsWeekly online queries from Yandex Russian users regarding smell impairment and levofloxacin were analysed in regions and large cities of Russia from 16 March 2020 to 21 February 2021.ResultsA strong positive direct correlation (r>0.7) was found between the number of smell-related queries in Yandex new cases of COVID-19 in 59 out of 85 Russian regions and large cities (70%). During the ‘first’ peak of COVID-19 incidence in Russia (April–May 2020), the increase in the number of smell-related queries outpaced the increase in new cases by 1–2 weeks in 23 out of 59 regions of Russia. During the ‘second’ peak of COVID-19 incidence in Russia (October–December 2020), the increase in the number of smell-related queries outpaced the increase in the number of new cases by 1–2 weeks in 36 regions of Russia, including Moscow. It was found that the query/new case ratio increased by more than 100% in 24 regions. The regions where the increase in queries was more than 160% compared with new infection cases during the ‘second’ peak of incidence demonstrated significantly higher search activity related to levofloxacin than the regions where the increase in queries was lower than 160% compared with the increase in new infection cases.ConclusionThe sudden interest in certain symptoms of COVID-19, such as smell impairment and the growing frequency of online queries among the population, can be used as an indicator of the spread of coronavirus infection among the population and for evaluation of the effectiveness of the COVID-19 epidemic control measures.
Alport syndrome is a genetic condition that results in hematuria, progressive renal impairment, hearing loss, and occasionally lenticonus and retinopathy. Approximately 80% of Alport syndrome cases ...are caused by X-linked mutations in the COL4A5 gene encoding type IV collagen. The objective of this study was to define the SNP profiles for COL4A5 in patients with hereditary nephritis and hematuria. For this, we examined four subjects from one Kazakh family clinically affected with X-linked Alport syndrome due to COL4A5 gene mutations. All 51 exons of the COL4A5 gene were screened by linkage analysis and direct DNA sequencing, resulting in the identification of a novel mutation (G641E) in exon 25. The mutation was found only in two affected family individuals but was not present in healthy family members or 200 unrelated healthy controls. This result demonstrates that this novel mutation is pathogenic and has meaningful implications for the diagnosis of patients with Alport syndrome.
Kazakhstan has been inhabited by different populations, such as the Kazakh, Kyrgyz, Uzbek and others. Here we investigate allelic and haplotypic polymorphisms of human leukocyte antigen (HLA) genes ...at DRB1, DQA1 and DQB1 loci in the Kazakh ethnic group, and their genetic relationship between world populations.
A total of 157 unrelated Kazakh ethnic individuals from Astana were genotyped using sequence based typing (SBT-Method) for HLA-DRB1, -DQA1 and -DQB1 loci. Allele frequencies, neighbor-joining method, and multidimensional scaling analysis have been obtained for comparison with other world populations. Statistical analyses were performed using Arlequin v3.11. Applying the software PAST v. 2.17 the resulting genetic distance matrix was used for a multidimensional scaling analysis (MDS). Respectively 37, 17 and 19 alleles were observed at HLA-DRB1, -DQA1 and -DQB1 loci. The most frequent alleles were HLA-DRB1*07:01 (13.1%), HLA-DQA1*03:01 (13.1%) and HLA-DQB1*03:01 (17.6%). In the observed group of Kazakhs DRB1*07:01-DQA1*02:01-DQB1*02:01 (8.0%) was the most common three loci haplotype. DRB1*10:01-DQB1*05:01 showed the strongest linkage disequilibrium. The Kazakh population shows genetic kinship with the Kazakhs from China, Uyghurs, Mongolians, Todzhinians, Tuvinians and as well as with other Siberians and Asians.
The HLA-DRB1, -DQA1 and -DQB1 loci are highly polymorphic in the Kazakh population, and this population has the closest relationship with other Asian and Siberian populations.
Behçet's disease (BD) as systemic vasculitis of unknown etiology is associated with HLA-B*51 in European and Asian populations. HLA-A*26 was claimed as an additional BD susceptibility marker in ...Japanese and Greek patients. This study was performed to test for HLA associations in HLA-B*51 negative German and Turkish BD populations.
In total, 65 German and 46 Turkish patients lacking HLA-B*51 were analyzed in comparison to healthy HLA-B*51 negative Germans (n = 1500) and Turks (n = 130). HLA-A/B genotypes were determined by SSOP. P-values with correction for multiple testing (p(c)), χ2-test and odds ratio (OR) were used for statistical evaluation.
HLA-A*26 was significantly more frequent in HLA-B*51- German patients p(c) = 0.0076, OR = 3.23, 95% CI 1.63 to 6.39 than in respective controls. HLA-A*26 was also elevated in a smaller group of Turkish patients versus the controls. Significant association of HLA-Bw4 with isoleucine at amino-acid position 80 (HLA-Bw4-80I) was found in the HLA-B*51(-) German cohort of BD patients p(c) = 0.0042, OR = 2.35, 95% CI 1.41 to 3.93) and in the Turkish patients in comparison to the respective controls p = 0.025, OR = 2.17, 95% CI 1.09 to 4.31. On the contrary, HLA-Bw4-80 T was reduced in both HLA-B*51(-) BD patient cohorts.
The study shows a significant association of HLA-Bw4-80I present on HLA-B*51 as well as on other B-locus molecules with BD. This indicates that distinctive Bw4 epitopes on HLA-B locus molecules could play a role in BD pathogenesis. The study also indicates an association with HLA-A*26 in German and Turkish BD patients as a genetic risk factor independent of HLA-B*51.
Kazakhstan is one of the 14 countries with a high rate of morbidity due to multidrug-resistant tuberculosis (MDR TB) in WHO European region. The aim of our study was to characterize mutations ...associated with drug resistance to rifampicin and isoniazid in Mycobacterium tuberculosis isolates from Kazakhstan. M. tuberculosis strains were isolated from TB patients in different regions of Kazakhstan. A drug susceptibility test was performed on Lowenstein-Jensen medium using the absolute concentration method. Sequencing analysis was performed of the rpoB rifampicin resistance-determining region and the katG gene, the oxyR-ahpC intergenic region, and the inhA promoter region in 259 MDR M. tuberculosis isolates, in 51 isoniazid-resistant isolates, and in 13 rifampicin-resistant isolates. The mutational analysis revealed that the most frequent mutations associated with rifampicin and isoniazid resistance in M. tuberculosis are the substitutions at codons 531 (82.7%) and 315 (98.4%) in the rpoB and katG genes, respectively. In addition, we have found mutations with lower frequency at codon 526 (8.4%), 533 (1.5%), and 516 (1.1%) in the rpoB gene. In 6.2% of the isolates, no mutations were found in the rpoB gene. The findings of this study provide useful data for a better understanding of the mutation spectrum of isoniazid and rifampicin resistance among strains isolated from patients in Kazakhstan. Our results are also useful for the development of diagnostic tests of MDR M. tuberculosis.
Biobanks are an important tool for clinical and research studies conducted on biomarkers of genetic therapy, diagnostic tests and new drugs; however, most biobanks remain incomplete and are often ...used without uniform standards and criteria. There is also a a lack of high-quality biological samples and many bioethical problems are often overlooked. Currently, Kazakhstan has no standard requirements and protocols for biomedical organizations. However, .an analysis of published data shows that possibly hundreds of samples are analyzed. Therefore, an establishment of biobank with standardized requirements could create better quality research. The National Center for Biotechnology has already started a biobank with more than 1,500 blood samples, with the ultimate goal of creating a biobank including around 10,000 blood samples of healthy volunteers, the same number of samples obtained from individuals with cardiovascular and endocrine diseases with samples stored under special conditions. The database contains demographic characteristics of donor's medical history. Informed consent for research received from all donors. This biobank can be considered as a national resource for scientific research.
Helicobacter pylori is an extra macro- and microdiverse bacterial species, but where and when diversity arises is not well-understood. To test whether a new environment accelerates H. pylori genetic ...changes for quick adaptation, we have examined the genetic and phenotypic changes in H. pylori obtained from different locations of the stomach from patients with early gastric cancer (ECG) or chronic gastritis (CG). Macroarray analysis did not detect differences in genetic content among all of the isolates obtained from different locations within the same stomach of patients with EGC or CG. The extent and types of functional diversity of H. pylori isolates were characterized by 2-D difference gel electrophoresis (2D DIGE). Our analysis revealed 32 differentially expressed proteins in H. pylori related to EGC and 14 differentially expressed proteins in H. pylori related to CG. Most of the differentially expressed proteins belong to the antioxidant protein group (SodB, KatA, AphC/TsaA, TrxA, Pfr), tricarbon acid cycle proteins (Idh, FrdA, FrdB, FldA, AcnB) and heat shock proteins (GroEL and ClpB). We conclude that H. pylori protein expression variability is mostly associated with microorganism adaptation to morphologically different parts of the stomach, which has histological features and morphological changes due to pathological processes; gene loss or acquisition is not involved in the adaptation process.
Alport syndrome is a type-IV collagen inherited disorder caused by mutations in COL4A3 and COL4A4 (autosomal recessive) or COL4A5 (X-linked). In our study, we describe the case of Alport syndrome in ...a Kazakh family. The 20-year-old male, born in 1993, was diagnosed with chronic nephritic syndrome when he was 16 years old. He had hearing loss and eye lesions. However, his maternal grandparents have not yet developed any kidney disease. They have normal vision and hearing. We have sequenced 51 exons of the COL4A5 gene in a total of 18 family members. The pedigree consists of three generations including 18 members (eight males and 10 females). We identied missense mutation 1226G>A in exon 20 of COL4A5 gene, causing amino acid substitutions of Gly to Asp at position 409.
Pharmacogenetic research in Kazakhstan Zholdybayeva, Elena; Iskakova, Aisha; Romanova, Aliya ...
Central Asian journal of global health,
01/2014, Letnik:
2, Številka:
Suppl
Journal Article
Recenzirano
Odprti dostop
Pharmacogenomics is an emerging field of medicine that combines genetics and pharmacology. Pharmacogenomic research is relatively new in Kazahkstan, but, in recent years, significant progress has ...been made in this field. The National Scientific Laboratory for Biotechnology has launched several government-funded research projects focused on finding genetic markers that determine susceptibility to various drugs. Another goal of pharmacogenetic research in the laboratory is to find the pharmacogenomic markers that target cardiovascular diseases, accounting for allelic frequencies in selected genes in the Kazakh population. In addition, pharmacogenomic testing kits allow patients to choose the drug dosage. For example, the drug Warfarin has been developed within the framework of the "Technology Commercialization Project," funded jointly by the Ministry of Education and Science of the Republic of Kazakhstan and the World Bank.
The pharmacogenomic studies were conducted using the real-time PCR and direct DNA sequencing. DNA was isolated from venous blood or buccal cells, collected from patients.
To date, we have identified the most promising areas of research in the field of pharmacogenomics in Kazakhstan. The allelic frequencies of a number of polymorphisms in the Kazakh population have been calculated (CYP2C9, CYP2C19, CYP3A4, VKORC1, CYP4F2, GGCX, CYP2D6, CYP1A2, NAT2, GSTP1, SLC47A1). A unique repository of DNA samples was established and is being replenished during the implementation of aforementioned projects. Development of the testing kit for individual selection of Warfarin dosage is nearing completion. A patent, named "Method of Selection Based Dose Warfarin Genotyping for the Kazakh Population" has been recently obtained. An application for another patent, titled "Express Method of Correction of Warfarin Dosing, Based on Real-time PCR" has received positive evaluation. The results of domestic pharmacogenomic studies will allow a more rational selection of drugs and their dosage regimens specific to the Kazakh population.
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