Publications by authors named "Ulan Kozhamkulov"

12 Publications

  • Page 1 of 1

Genetic factors associated with obesity risks in a Kazakhstani population.

BMJ Nutr Prev Health 2021 5;4(1):90-101. Epub 2021 Feb 5.

School of Medicine, Nazarbayev University, Nur-Sultan, Kazakhstan.

Objectives: There is limited published literature on the genetic risks of chronic inflammatory related disease (eg, obesity and cardiovascular disease) among the Central Asia population. The aim is to determine potential genetic loci as risk factors for obesity for the Kazakhstani population.

Setting: Kazakhstan.

Participants: One hundred and sixty-three Kazakhstani nationals (ethnic groups: both Russians and Kazakhs) were recruited for the cross-sectional study. Linear regression models, adjusted for confounding factors, were used to examine the genetic associations of single nucleotide polymorphisms (SNPs) in 19 genetic loci with obesity (73 obese/overweight individuals and 90 controls).

Results: Overall, logistic regression analyses revealed genotypes C/T in CRP (rs1205), A/C in AGTR1 (rs5186), A/G in CBS (rs234706), G/G in FUT2 (rs602662), A/G in PAI-1 (rs1799889), G/T (rs1801131) and A/G (rs1801133) in MTHFR genes significantly decrease risk of overweight/obesity. After stratification for ethnicity, rs234706 was significantly associated with overweight/obesity in both Russians and Kazakhs, while rs1800871 was significant in Kazakhs only.

Conclusions: This study revealed that variations in SNPs known to be associated with cardiovascular health can also contribute to the risks of developing obesity in the population of Kazakhstan.
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http://dx.doi.org/10.1136/bmjnph-2020-000139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258080PMC
February 2021

Stapleless vs Stapled Gastric Bypass vs Hypocaloric Diet: a Three-Arm Randomized Controlled Trial of Body Mass Evolution with Secondary Outcomes for Telomere Length and Metabolic Syndrome Changes.

Obes Surg 2021 07 8;31(7):3165-3176. Epub 2021 May 8.

Research Group of the University Medical Center, Nur-Sultan, Kazakhstan.

Background: Obesity and metabolic syndrome (MetS) reduce life expectancy and are challenging to resolve. This randomized controlled trial (RCT) of patients with obesity and MetS undergoing surgical vs nonsurgical treatment compared changes in BMI, and secondarily, telomere length (as a biomarker of life expectancy) and changes in MetS components (insulin resistance, dyslipidemia, hypertension).

Methods: Study design was a single-center, prospective, three-arm RCT. Group 1 patients underwent novel unstapled laparoscopic one anastomosis gastric bypass with an obstructive stapleless pouch and anastomosis (LOAGB-OSPAN); Group 2, stapled laparoscopic mini-gastric bypass-one anastomosis gastric bypass (LMGB-OAGB); and Group 3, nonsurgical weight loss therapy via a hypocaloric diet with energy restriction (HDER). The primary outcome measure was change in BMI; secondary outcome measures included change in leukocyte telomere length and other MetS components.

Results: Of 96 participants screened, 60 were randomly allocated to 3 groups: LOAGB-OSPAN group (n = 20), LMGB-OAGB group (n = 20), and HDER group (n = 20). At post-treatment month 12, respective BMI changes: BMI -12.13 (-8.34, -15.93); -16.04 (-11.7, 20.37); -2,76 (-3.84, -9.36) (p < 0.01). The two surgical groups experienced significant change in telomere length: LOAGB-OSPAN 2.02 (1.61, 2.41), p = 0.001; LMGB-OAGB 2.07 (1.72, 2.43), p = 0.001; and HDER 0.28 (0.22, 0.78), p = 0.26. The surgical groups were also more effective in treating MetS components. There were no deaths. Adverse events: LOAGB-OSPAN (n = 2) (Clavien-Dindo grade II); LMGB-OAGB (n = 8) (grade I (n = 6) and grade II (n = 2).

Conclusions: Compared with hypocaloric diet therapy, both bariatric procedures resulted in greater BMI loss, and secondarily, a significant increase in telomere length, and greater MetS resolution.

Trial Registration: ClinicalTrials.gov , NCT03667469, registered on 11 September 2018.
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http://dx.doi.org/10.1007/s11695-021-05454-2DOI Listing
July 2021

Patients with coronary heart disease, dilated cardiomyopathy and idiopathic ventricular tachycardia share overlapping patterns of pathogenic variation in cardiac risk genes.

PeerJ 2021 19;9:e10711. Epub 2021 Jan 19.

Laboratory of Genomic and Personalized Medicine, Center for Life Science, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan.

Background: Ventricular tachycardia (VT) is a major cause of sudden cardiac death (SCD). Clinical investigations can sometimes fail to identify the underlying cause of VT and the event is classified as idiopathic (iVT). VT contributes significantly to the morbidity and mortality in patients with coronary artery disease (CAD) and dilated cardiomyopathy (DCM). Since mutations in arrhythmia-associated genes frequently determine arrhythmia susceptibility screening for disease-predisposing variants could improve VT diagnostics and prevent SCD in patients.

Methods: Ninety-two patients diagnosed with coronary heart disease (CHD), DCM, or iVT were included in our study. We evaluated genetic profiles and variants in known cardiac risk genes by targeted next generation sequencing (NGS) using a newly designed custom panel of 96 genes. We hypothesized that shared morphological and phenotypical features among these subgroups may have an overlapping molecular base. To our knowledge, this was the first study of the deep sequencing of 96 targeted cardiac genes in Kazakhstan. The clinical significance of the sequence variants was interpreted according to the guidelines developed by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015. The ClinVar and Varsome databases were used to determine the variant classifications.

Results: Targeted sequencing and stepwise filtering of the annotated variants identified a total of 307 unique variants in 74 genes, totally 456 variants in the overall study group. We found 168 mutations listed in the Human Genome Mutation Database (HGMD) and another 256 rare/unique variants with elevated pathogenic potential. There was a predominance of high- to intermediate pathogenicity variants in , , , , and in CHD VT patients. Similar frequencies were observed in DCM VT, and iVT patients, pointing to a common molecular disease association. and contained the most variants in the three subgroups which confirm the impact of these genes in the complex pathogenesis of cardiomyopathies and VT. The classification of 307 variants according to ACMG guidelines showed that nine (2.9%) variants could be classified as pathogenic, nine (2.9%) were likely pathogenic, 98 (31.9%) were of uncertain significance, 73 (23.8%) were likely benign, and 118 (38.4%) were benign. CHD VT patients carry rare genetic variants with increased pathogenic potential at a comparable frequency to DCM VT and iVT patients in genes related to sarcomere function, nuclear function, ion flux, and metabolism.

Conclusions: In this study we showed that in patients with VT secondary to coronary artery disease, DCM, or idiopathic etiology multiple rare mutations and clinically significant sequence variants in classic cardiac risk genes associated with cardiac channelopathies and cardiomyopathies were found in a similar pattern and at a comparable frequency.
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http://dx.doi.org/10.7717/peerj.10711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821765PMC
January 2021

Whole-genome sequencing data of Kazakh individuals.

BMC Res Notes 2021 Feb 4;14(1):45. Epub 2021 Feb 4.

School of Medicine, Nazarbayev University, Nur-Sultan, Kazakhstan.

Objectives: Kazakhstan is a Central Asian crossroad of European and Asian populations situated along the way of the Great Silk Way. The territory of Kazakhstan has historically been inhabited by nomadic tribes and today is the multi-ethnic country with the dominant Kazakh ethnic group. We sequenced and analyzed the whole-genomes of five ethnic healthy Kazakh individuals with high coverage using next-generation sequencing platform. This whole-genome sequence data of healthy Kazakh individuals can be a valuable reference for biomedical studies investigating disease associations and population-wide genomic studies of ethnically diverse Central Asian region.

Data Description: Blood samples have been collected from five ethnic healthy Kazakh individuals living in Kazakhstan. The genomic DNA was extracted from blood and sequenced. Sequencing was performed on Illumina HiSeq2000 next-generation sequencing platform. We sequenced and analyzed the whole-genomes of ethnic Kazakh individuals with the coverage ranging from 26 to 32X. Ranging from 98.85 to 99.58% base pairs were totally mapped and aligned on the human reference genome GRCh37 hg19. Het/Hom and Ts/Tv ratios for each whole genome ranged from 1.35 to 1.49 and from 2.07 to 2.08, respectively. Sequencing data are available in the National Center for Biotechnology Information SRA database under the accession number PRJNA374772.
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http://dx.doi.org/10.1186/s13104-021-05464-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863413PMC
February 2021

Association of rs12722 COL5A1 with pulmonary tuberculosis: a preliminary case-control study in a Kazakhstani population.

Mol Biol Rep 2021 Jan 7;48(1):691-699. Epub 2021 Jan 7.

School of Medicine, Nazarbayev University, Nur-Sultan city, Kazakhstan.

Lung cavitation is the classic hallmark of TB, which facilitates the disease development and transmission. It involves the degradation of lung parenchyma which is mainly made up of collagen fibers by metalloproteinases (MMPs) produced by activated monocyte-derived cells, neutrophils and stromal cells. The following population-based preliminary case-control study of adults with TB (50) and controls (112) without TB was used to investigate possible association between rs1800012 in COL1A1, rs12722 in COL5A1 genes and pulmonary TB in Kazakhstan. We examined 162 samples (50 cases and 112 controls) to study the associations between TB disease status and demographic variables along with single nucleotide polymorphisms related to COLA1 and COL5A1. The unadjusted χ2 and multivariable logistic regression was performed to find out relationships between SNP and other predictors. Preliminary findings suggest that there is a statistically significant association of age (AOR = 0.97, 95% CI:0.94-0.99, p value = 0.049), social status (AOR = 2.41, 95% CI:1.16-5.02, p value = 0.018), HIV status (AOR = 7.12, 95% CI:1.90-26.7, p value = 0.004) and heterozygous rs12722 SNP (AOR = 2.47, 95% CI:1.17-5.19, p value = 0.018) polymorphism of COL5A1 gene with TB susceptibility. The association of collagen genes with TB pathogenesis indicates that anti TB programs can include development of new drug regimens that include MMP inhibitors which has been found to be helpful in collagen remodeling and repair. Therapeutic targeting of MMPs will prevent extracellular matrix and collagen degradation and granuloma maturation.
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http://dx.doi.org/10.1007/s11033-020-06121-yDOI Listing
January 2021

Whole genome sequence data of XDR strain, isolated from patient in Kazakhstan.

Data Brief 2020 Dec 17;33:106416. Epub 2020 Oct 17.

Laboratory of Bioinformatics and Systems Biology, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Nur-Sultan 010000, Kazakhstan.

Drug-resistant tuberculosis (TB) is a major public health problem. Clinical (MTB) isolate with Extensively drug-resistant tuberculosis (MTB-XDR) profile was subjected to whole-genome sequencing using a next-generation sequencing platform (NGS) Roche 454 GS FLX+ followed by bioinformatics sequence analysis. Quality of read was checked by FastQC, paired-end reads were trimmed using Trimmomatic. genome assembly was conducted using Velvet v.1.2.10. The assembled genome of XDR-TB-1599 strain was functionally annotated using the PATRIC platform. Analysis of assembled genome was performed using ResFinder, CARD, CASTB and TB-Profiler tools. MIRU_VNTR genotyping on 12 loci and spoligotyping have been performed for XDR-TB-1599 isolate. XDR-TB-1599 strain yielded an average read depth of 21-fold with overall 4 199 325 bp. The assembled genome contains 5528 protein-coding genes, including key drug resistance and virulence-associated genes and GC content of 65.4%. We identified that all proteins encoded by this strain contain conserved domains associated with the first-line anti-tuberculosis drugs such as rifampicin, isoniazid, streptomycin and ethionamide. TB-Profiler had higher average concordance results with phenotypic DST (drug susceptibility testing) in comparison with ResFinder, CARD, CASTB profiling to first-line (75% vs 50%) and second-line (25% vs 0%) of anti-TB drugs, correspondingly. To our knowledge, this is the first report of a highly annotated and characterized whole-genome sequence and assembled XDR-TB strain isolated from a sputum of new TB case-patient from Kazakhstan performed on Roche 454 GS FLX+ platform. This report highlights an important role of whole-genome sequencing technology and analysis as an advanced approach for drug-resistance investigations of circulated TB isolates.
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http://dx.doi.org/10.1016/j.dib.2020.106416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578676PMC
December 2020

Association of genetic variations in the vitamin D pathway with susceptibility to tuberculosis in Kazakhstan.

Mol Biol Rep 2020 Mar 13;47(3):1659-1666. Epub 2020 Jan 13.

Department of Biomedical Sciences, School of Medicine, Nazarbayev University, 010000, Nur-Sultan, Kazakhstan.

Tuberculosis (TB) poses an important health challenge and a significant economic burden for Kazakhstan and in Central Asia. Recent findings show a number of immunological related processes and host Mycobacterium tuberculosis defense are impacted by a variety of genes of the human host including those that play a part in the vitamin D metabolism. We investigated the genetic variation of genes in the vitamin D metabolic pathway of a cohort 50 TB cases in Kazakhstan and compared them to 34 controls living in the same household with someone infected with TB. We specifically analyzed 11 SNPs belonging to the following genes: DHCR7, CYP2R1, GC-1, CYP24A1, CYP27A1, CYP27B1, VDR and TNFα. These genes play a number of different roles including synthesis, activation, delivery and binding of the activated vitamin D. Our preliminary results indicate significant association of VDR (vitamin D receptor) SNPs (rs1544410, BsmI, with OR = 0.425, CI 0.221-0.816, p = 0.009 and rs731236, TaqI with OR = 0.443, CI 0.228-0.859, p = 0.015) and CYP24A1 (rs6013897 with OR = 0.436, CI 0.191-0.996, p = 0.045) with TB. Interaction of genetic variation of VDR and CYP24A1 may impact susceptibility to TB. The findings provided initial clues to understand individual genetic differences in relation to susceptibility and protection to TB.
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http://dx.doi.org/10.1007/s11033-020-05255-3DOI Listing
March 2020

Identifying risk factors associated with smear positivity of pulmonary tuberculosis in Kazakhstan.

PLoS One 2017 1;12(3):e0172942. Epub 2017 Mar 1.

Columbia University Mailman School of Public Health, Department of Epidemiology, New York, NY, United States of America.

Background: Sputum smear-positive tuberculosis (TB) patients have a high risk of transmission and are of great epidemiological and infection control significance. Little is known about the smear-positive populations in high TB burden regions, such as Kazakhstan. The objective of this study is to characterize the smear-positive population in Kazakhstan and identify associated modifiable risk factors.

Methods: Data on incident TB cases' (identified between April 2012 and March 2014) socio-demographic, risk behavior, and comorbidity characteristics were collected in four regions of Kazakhstan through structured survey and medical record review. We used multivariable logistic regression to determine factors associated with smear positivity.

Results: Of the total sample, 193 (34.3%) of the 562 study participants tested smear-positive. In the final adjusted multivariable logistic regression model, sex (adjusted odds ratio (aOR) = 2.0, 95% CI:1.3-3.1, p < 0.01), incarceration (aOR = 3.6, 95% CI:1.2-11.1, p = 0.03), alcohol dependence (aOR = 2.6, 95% CI:1.2-5.7, p = 0.02), diabetes (aOR = 5.0, 95% CI:2.4-10.7, p < 0.01), and physician access (aOR = 2.7, 95% CI:1.3-5.5p < 0.01) were associated with smear-positivity.

Conclusions: Incarceration, alcohol dependence, diabetes, and physician access are associated with smear positivity among incident TB cases in Kazakhstan. To stem the TB epidemic, screening, treatment and prevention policies should address these factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172942PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332099PMC
August 2017

Draft Genome Sequences of Two Clinical Isolates of Mycobacterium tuberculosis from Sputum of Kazakh Patients.

Genome Announc 2015 May 14;3(3). Epub 2015 May 14.

Department of Genomic and Personalized Medicine, Center for Life Sciences, Nazarbayev University, Astana, Kazakhstan

Here, we report the draft genome sequences of two clinical isolates of Mycobacterium tuberculosis (MTB-476 and MTB-489) isolated from sputum of Kazakh patients.
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http://dx.doi.org/10.1128/genomeA.00466-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432342PMC
May 2015

Distribution of Beijing Genotype Among Clinical Isolates of Circulating in Kazakhstan.

Cent Asian J Glob Health 2014 12;3(Suppl):145. Epub 2014 Dec 12.

Center for Life Sciences, Nazarbayev University, Astana, Kazakhstan.

Introduction: Methods of genotyping of M. tuberculosis play an important role in tuberculosis (TB) infection control. These techniques are used to detect or exclude laboratory errors, control recurrent cases, and determine ways of TB transmission. Today, there are more than 10 methods of genotyping; MIRU-VNTR is one of the most widely used methods in the world. In this study we aimed to estimate biological diversity of clinical isolates of M. tuberculosis from different regions of Kazakhstan based on MIRU-VNTR analysis.

Materials And Methods: MIRU-VNTR was used to genotype 134 clinical isolates of M. tuberculosis isolated from new cases and recurrent cases of TB from different regions of Kazakhstan. Amplification was done using 15 MIRU-VNTR loci. Determination of the number of tandem repeats in the corresponding locus was performed via Quantity One v.4.4.0 (BioRad, USA) software. H37Rv (NC_000962) reference strain was used as a positive control.

Results: Phylogenic tree was built using www.miru-vntr.org web-resource based on the results of MIRU-VNTR analysis. Beijing family strains associated with drug resistance to antituberculosis drugs were prevalent among all isolates of M. tuberculosis circulating in Kazakhstan. Strains of the Beijing genotype were prevalent in both new cases (65%) and recurrent cases (89.4%) of tuberculosis. The second meaningful genotype that is spread in the territory of Kazakhstan is LAM, the frequency of distribution is 7.3% in new and 4.5% in recurrent cases. Other families of M. tuberculosis such as Ural, Haarlem, CAS, NEW-1, S were found in less than 4% of cases.

Conclusion: Prevalence of Beijing family strains among all isolates of M. tuberculosis from different regions of Kazakhstan was shown. Strains of this family are prevalent among young people. This genotype is responsible for ongoing TB transmission in the present time. This genotype is more virulent; therefore, investigation of the epidemiology of the Beijing genotype plays crucial role in the monitoring of tuberculosis.
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http://dx.doi.org/10.5195/cajgh.2014.145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960921PMC
December 2014

Whole genome sequencing of M.tuberculosis in Kazakhstan: preliminary data.

Cent Asian J Glob Health 2013 27;2(Suppl):121. Epub 2014 Mar 27.

Center for Life Sciences, Nazarbayev University, Astana, Kazakhstan.

Background: Tuberculosis is a major public health problem which infects one third of the world's population, resulting in more than two million deaths every year. The emergence of whole genome sequencing (WGS) technologies as a primary research tool has allowed for the detection of genetic diversity in Mycobacterium tuberculosis (MTB) with unprecedented resolution. WGS has been used to address a broad range of topics, including the dynamics of evolution, transmission, and treatment. To our knowledge, studies involving WGS of Kazakhstani strains of M. tuberculosis have not yet been performed.

Aim: To perform whole genome sequencing of M. tuberculosis strains isolated in Kazakhstan and analyze sequence data (first experience and preliminary data).

Results: In the present report, we announce the whole-genome sequences of the two clinical isolates of Mycobacterium tuberculosis, MTB-489 and MTB-476, isolated from the Almaty region. These strains were part of a repository that was created during our project "Creating prerequisites of personalized approach in the diagnosis and treatment of tuberculosis, based on whole genome-sequencing of M. tuberculosis". Two strains were isolated from sputum samples of patients P1 and P2. Phenotypically, two isolates were drug-susceptible M. tuberculosis. Sequence data was compared with the publicly available data on M. tuberculosis laboratory strain H37Rv and others. The sequencing of the strains was performed on a Roche 454 GS FLX+ next-generation sequencing platform using a standard protocol for a shotgun genome library. The whole genome sequencing was performed for two isolates MTB-476 and MTB-489. 96 M bp with an average read length of 520 bp, approximately 21.8X coverage and 104.2 M bp with an average read length of 589 bp and approximately 23.7X coverage were generated for the MTB-476 and MTB-489, respectively. The genome of MTB-476 consists of 257 contigs, 4204 CDS, 46 tRNAs and 3 rRNAs. MTB-489 has 187 contigs, 4183 CDS, 45 tRNAs and 3rRNAs.

Conclusion: The results of genome assembling have been submitted into NCBI GenBank and are available for public access under the accession numbers AZBA00000000 and AZAZ00000000. These genome assemblies can be useful for comparative genome analysis and for identification of novel SNPs and gene variants in genomes of M.tuberculosis.
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http://dx.doi.org/10.5195/cajgh.2013.121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960904PMC
March 2014

Molecular characterization of rifampicin- and isoniazid-resistant Mycobacterium tuberculosis strains isolated in Kazakhstan.

Jpn J Infect Dis 2011 ;64(3):253-5

National Center for Biotechnology, Astana, Republic of Kazakhstan.

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.
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September 2011
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