Mitochondrial and Y-chromosomal profile of the Kazakh population from East Kazakhstan

Aim To study the genetic relationship of Kazakhs from East Kazakhstan to other Eurasian populations by examining paternal and maternal DNA lineages. Methods Whole blood samples were collected in 2010 from 160 unrelated healthy Kazakhs residing in East Kazakhstan. Genomic DNA was extracted with Wizard® genomic DNA Purification Kit. Nucleotide sequence of hypervariable segment I of mitochondrial DNA (mtDNA) was determined and analyzed. Seventeen Y-short tandem repeat (STR) loci were studied in 67 samples with the Amp- FiSTR Y-filer PCR Amplification Kit. In addition, mtDNA data for 2701 individuals and Y-STR data for 677 individuals were retrieved from the literature for comparison. Results There was a high degree of genetic differentiation on the level of mitochondrial DNA. The majority of maternal lineages belonged to haplogroups common in Central Asia. In contrast, Y-STR data showed very low genetic diversity, with the relative frequency of the predominant haplotype of 0.612. Conclusion The results revealed different migration patterns in the population sample, showing there had been more migration among women. mtDNA genetic diversity in this population was equivalent to that in other Central Asian populations. Genetic evidence suggests the existence of a single paternal founder lineage in the population of East Kazakhstan, which is consistent with verbal genealogical data of the local tribes

BRCA1 and BRCA2 Gene Mutations Screening In Sporadic Breast Cancer Patients In Kazakhstan.

Background: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Kazakhstan women.Aim: To evaluate the role of BRCA1/2 mutations in Kazakhstan women presenting with sporadic breast cancer.Methods: We investigated the distribution and nature of polymorphisms in BRCA1 and BRCA2 entire coding regions in 156 Kazakhstan sporadic breast cancer cases and 112 age-matched controls using automatic direct sequencing.Results: We identified 22 distinct variants, including 16 missense mutations and 6 polymorphisms in BRCA1/2 genes. In BRCA1, 9 missense mutations and 3 synonymous polymorphisms were observed. In BRCA2, 7 missense mutations and 3 polymorphisms were detected. There was a higher prevalence of observed mutations in Caucasian breast cancer cases compared to Asian cases (p<0.05); higher frequencies of sequence variants were observed in Asian controls. No recurrent or founder mutations were observed in BRCA1/2 genes. There were no statistically significant differences in age at diagnosis, tumor histology, size of tumor, and lymph node involvement between women with breast cancer with or without the BRCA sequence alterations.Conclusions:Considering the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of BRCA1/2 mutations and reliable genetic counseling for Kazakhstan sporadic breast cancer patients. Evaluation of common polymorphisms and mutations and breast cancer risk in families with genetic predisposition to breast cancer is ongoing in another current investigation.

GENETIC VARIANTS, METABOLOME, AND GUT MICROBIOME BIOMARKERS FOR OBESITY AND AGING IN RANDOMLY SELECTED KAZAKH INDIVIDUALS

Objective: Metabolic syndrome (MS) is a cluster of inter-related and heritable metabolic traits, which collectively impart unsurpassed risk for atherosclerotic cardiovascular disease and type 2diabetes. Considerable work has been done to understand the underlying disease mechanisms by elucidating its genetic etiology. Genome, Metabolome variations and gut microbiome can predict disease risk and diagnosis and help to understand molecular pathophysiology. We aimed toassess plasma metabolom differences and gut microbiome as well as genetic variants among Kazakh population to identify and characterize the genetic, metabolic profiles and host-gut microbiota interactions. Methods: Kazakhs were recruited into study after signing of informed consent in Astana, Kazakhstan. Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS) (Metabolon, USA) and NGS16S rRNA gene-sequence-based methods were used. Bioinformatic and statistical analyses were performed. Results: Subjects were stratified by age (young <45y, old ≥45y), gender and BMI. 853 different biochemical indicators of the main pathways for the metabolism were identified in plasma. Results demonstrate alterations in various metabolic pathways in older participants compared to younger subjects. Metabolic differences included changes in metabolites associated with the metabolism of fatty acids, steroidogenesis, secondary carnitine metabolism, inflammation and oxidative stress. Microbiomes of older persons are characterized by a high level of microorganisms involved in the processing of plant substrates, butyrate- producing bacteria and also has higher values of opportunistic microorganisms, representatives of the Tenericutes family. The biodiversity index of the microbiome of older persons is reduced in comparison with the biodiversity index in younger participants. This may indicate the influence on the microbiome characteristics of such factors as genotype, nutrition, lifestyle.Genetic risk factors associated with the obesity and hypertension were identified. Conclusions: Understanding plasma metabolome and gut microbiome is essential to the development of future personalized strategies of healthcare. Genome-wide association studies (GWAS) have been widely utilized albeit with modest success in identifying variants that are associated with more than two metabolic traits. Further studies with detailed analysis are needed to clarify host-gut genetic and metbolome interactions. Study was supported by a grant from the Ministry Education and Science, Republic of Kazakhstan (BR05236508)

THE EVALUATION OF CHROMOSOME TELOMERE LENGTH CHANGE AS A CRITERION OF LIFE EXPECTANCY IN BARIATRIC PRACTICE

In recent decades, the prevalence of obesity has been steadily increasing in most countries of the world. Overweight is a risk factor for a wide range of endocrine, cardiovascular, gastrointestinal, metabolic, neoplastic and musculoskeletal disorders and diseases. As you know, obesity is a state of chronic inflammation and severe oxidative stress, which will certainly affect the length of the chromosome telomeres. The dynamics of telomere length changes plays a decisive role in the regulation of cellu lar processes and cellular changes. Damage to telomeres, chromatin structures that help maintain the stability of the genome, leads to cell death or aging. However, information on how telomere length changes after weight loss through bariatric surgery remains limited to date. There are several types of bariatric surgery, each of which has its advantages and disadvantages. Based on this, it is possible that the restoration of the telomere length will differ depending on the technique used. This review de scribes the mechanisms for shortening leukocyte telomeres, and how bariatric surgery can affect this. The review also includes an analysis of evidence linking obesity and accelerated aging processes, as they are regulated by telomere

ASSOCIATION OF GENETIC POLYMORPHISMS WITH COMPLICATIONS OF IMPLANTED LVAD DEVICES IN PATIENTS WITH CONGESTIVE HEART FAILURE: A KAZAKHSTANI STUDY

The left ventricular assist device (LVAD) is one of the alternative treatments for heart failure (HF) patients. However, LVAD support is followed by thrombosis, and bleeding complications which are caused by high non-physiologic shear stress and antithrombotic/anticoagulant therapy. A high risk of complications occurs in the presence of the genotype polymorphisms which are involved in the coagulation system, hemostasis function and in the metabolism of the therapy. The aim of the study was to investigate the influence of single-nucleotide polymorphisms (SNP) in HF patients with LVAD complications. We analyzed 21 SNPs in HF patients (n = 98) with/without complications, and healthy controls (n = 95). SNPs rs9934438; rs9923231 in VKORC1, rs5918 in ITGB3 and rs2070959 in UGT1A6 demonstrated significant association with HF patients’ complications (OR (95% CI): 3.96 (1.42–11.02), p = 0.0057), (OR (95% CI): 3.55 (1.28–9.86), p = 0.011), (OR (95% CI): 5.37 (1.79–16.16), p = 0.0056) and OR (95% CI): 4.40 (1.06–18.20), p = 0.044]. Genotype polymorphisms could help to predict complications at pre- and post-LVAD implantation period, which will reduce mortality rate. Our research showed that patients can receive treatment with warfarin and aspirin with a personalized dosage and LVAD complications can be predicted by reference to their genotype polymorphisms in VKORC1, ITGB3 and UGT1A6 genes

BRCA1 and BRCA2 Gene Mutations Screening In Sporadic Breast Cancer Patients In Kazakhstan.

Background: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Kazakhstan women. Aim: To evaluate the role of BRCA1/2 mutations in Kazakhstan women presenting with sporadic breast cancer. Methods: We investigated the distribution and nature of polymorphisms in BRCA1 and BRCA2 entire coding regions in 156 Kazakhstan sporadic breast cancer cases and 112 age-matched controls using automatic direct sequencing. Results: We identified 22 distinct variants, including 16 missense mutations and 6 polymorphisms in BRCA1/2 genes. In BRCA1, 9 missense mutations and 3 synonymous polymorphisms were observed. In BRCA2, 7 missense mutations and 3 polymorphisms were detected. There was a higher prevalence of observed mutations in Caucasian breast cancer cases compared to Asian cases (p<0.05); higher frequencies of sequence variants were observed in Asian controls. No recurrent or founder mutations were observed in BRCA1/2 genes. There were no statistically significant differences in age at diagnosis, tumor histology, size of tumor, and lymph node involvement between women with breast cancer with or without the BRCA sequence alterations. Conclusions:Considering the majority of breast cancer cases are sporadic, the present study will be helpful in the evaluation of the need for the genetic screening of BRCA1/2 mutations and reliable genetic counseling for Kazakhstan sporadic breast cancer patients. Evaluation of common polymorphisms and mutations and breast cancer risk in families with genetic predisposition to breast cancer is ongoing in another current investigation

Polymorphisms of HLA-DRB1, -DQA1 and -DQB1 in inhabitants of Astana, the capital city of Kazakhstan.

BackgroundKazakhstan 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.Methodology/principal findingsA 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.Conclusions/significanceThe 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

Haplotype frequency and significant linkage disequilibrium parameter of HLA two-loci haplotypes in Kazakh population (Astana).

a<p>Number of times;</p>b<p>Haplotype frequency;</p>c<p>D Linkage disequilibrium;</p>d<p>Only t values ≥ 2.0 were considered significant.</p><p>Haplotype frequency and significant linkage disequilibrium parameter of HLA two-loci haplotypes in Kazakh population (Astana).</p

Territory of the Republic of Kazakhstan.

<p>Territory of the Republic of Kazakhstan.</p