Genetic markers of cardiac autonomic neuropathy in the Kazakh population.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes. MATERIALS AND METHODS: A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0. RESULTS: Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively). CONCLUSION: The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.

Genetic polymorphism of 27 Y-STR loci in Kazakh populations from Central Kazakhstan.

BACKGROUND: The haplotypes from Northern, Southern, Eastern, and Western Kazakhstan, analysed for 27 Y-STR loci, have been contributed to the Y-Chromosome STR Haplotype Reference Database, while the genetic profile of Central Kazakhstan remains inadequately explored. AIM: To investigate the genetic diversity of 27 Y-STR loci in the Kazakh populations from Central Kazakhstan. SUBJECTS AND METHODS: A total of 112 unrelated Central Kazakh males were genotyped via the Yfiler Plus kit. Data analysis yielded haplotype and allele frequencies, and forensic parameters. Genetic distances were graphically represented by a multidimensional scaling plot, with genetic linkages further elucidated through Nei's distance dendrograms and Median-joining networks. RESULTS: A total of 102 haplotypes were detected, of which 96 were unique. The haplotype diversity and discrimination capacity were 0.997 and 0.91, respectively. Central Kazakhstan displays a unique cluster in analyses, underscoring its distinct Y-chromosome diversity compared to other Kazakh regions. The analysis of the Naiman tribe, predominantly residing in Central, Southern and Eastern Kazakhstan, revealed three genetic clusters of distinct haplogroups associated with their clans. CONCLUSIONS: The identified haplotypes will enhance the existing reference database for Y-chromosomal studies in Kazakhstan, offering a robust tool for future research in population genetics, forensic science and genetic genealogy.

Genetic polymorphism of Y-chromosome in Kazakh populations from Southern Kazakhstan.

BACKGROUND: The Kazakhs are one of the biggest Turkic-speaking ethnic groups, controlling vast swaths of land from the Altai to the Caspian Sea. In terms of area, Kazakhstan is ranked ninth in the world. Northern, Eastern, and Western Kazakhstan have already been studied in relation to genetic polymorphism 27 Y-STR. However, current information on the genetic polymorphism of the Y-chromosome of Southern Kazakhstan is limited only by 17 Y-STR and no geographical study of other regions has been studied at this variation. RESULTS: The Kazakhstan Y-chromosome Haplotype Reference Database was expanded with 468 Kazakh males from the Zhambyl and Turkestan regions of South Kazakhstan by having their 27 Y-STR loci and 23 Y-SNP markers analyzed. Discrimination capacity (DC = 91.23%), haplotype match probability (HPM = 0.0029) and haplotype diversity (HD = 0.9992) are defined. Most of this Y-chromosome variability is attributed to haplogroups C2a1a1b1-F1756 (2.1%), C2a1a2-M48 (7.3%), C2a1a3-F1918 (33.3%) and C2b1a1a1a-M407 (6%). Median-joining network analysis was applied to understand the relationship between the haplotypes of the three regions. In three genetic layer can be described the position of the populations of the Southern region of Kazakhstan-the geographic Kazakh populations of Kazakhstan, the Kazakh tribal groups, and the people of bordering Asia. CONCLUSION: The Kazakhstan Y-chromosome Haplotype Reference Database was formed for 27 Y-STR loci with a total sample of 1796 samples of Kazakhs from 16 regions of Kazakhstan. The variability of the Y-chromosome of the Kazakhs in a geographical context can be divided into four main clusters-south, north, east, west. At the same time, in the genetic space of tribal groups, the population of southern Kazakhs clusters with tribes from the same region, and genetic proximity is determined with the populations of the Hazaras of Afghanistan and the Mongols of China.

Genetic polymorphism of 27 Y-STR loci in Kazakh populations from Eastern Kazakhstan.

BACKGROUND: The establishment of a national haplotype database is important for forensic and genetic applications and requires studying genetic polymorphisms at Y-STR sites. However, the genetic structure of the Eastern Kazakhstan population is poorly characterised. AIM: To investigate the genetic polymorphisms of 27 Y-STR loci in the Kazakh population from Eastern Kazakhstan and analyse the population genetic relationships of the Eastern Kazakhs with other populations. SUBJECTS AND METHODS: The Yfiler Plus kit was utilised to genotype 246 healthy, unrelated males from Eastern Kazakhstan. Based on the raw data, haplotype and allele frequencies along with forensic parameters were calculated, and an MDS plot was constructed. RESULTS: A total of 207 haplotypes were detected, of which 186 were unique. The haplotype diversity and discrimination capacity were 0.997 and 0.841, respectively. Population comparisons showed that Eastern Kazakhs have close genetic relationships with Kazakhs from Xinjiang, China. At the same time, a difference was found between the studied population and the previous one in the same part of Kazakhstan. CONCLUSIONS: The obtained haplotypes will help to expand the Kazakhstan Y-chromosome reference database and will be useful for future genetic research and forensic applications.

Risk factors for aneurysm rupture among Kazakhs: findings from a national tertiary.

BACKGROUND: Rupture of intracranial aneurysms (RIA) leads to subarachnoid hemorrhage (SAH) with severe consequences. Although risks for RIA are established, the results vary between ethnic groups and were never studied in Kazakhstan. This study aimed to establish the risk factors of RIA in the Kazakh population.  METHODS: Retrospective analysis of 762 patients with single IAs, who attended the neurosurgical center from 2008 until 2018, was conducted. Demographic characteristics, such as age, sex, smoking status, and hypertension were considered. Descriptive and bivariate analyses were performed. A multivariable logistic regression model was built to identify factors correlated with RIA. RESULTS: The mean age of participants was 48.49 ± 0.44 years old. The majority (68.37%) of IAs have ruptured. Of the ruptured aneurysms, 43.76% were < 6 mm, and 38.39% were located on the anterior cerebral and anterior communicating arteries (ACA). Logistic regression model indicates younger age group (16-40 years), smoking, having stage 3 hypertension, smaller IA size and its location on ACA increase the odds of rupture. CONCLUSIONS: This study has revealed that younger, smoking patients with stage 3 arterial hypertension are at higher risk for RIA. Small aneurysms (< 6 mm) and location on ACA had increased odds of rupture, while larger aneurysms on internal carotid arteries had lower odds.

Genetic polymorphism of 27 Y-STR loci in Kazakh populations from Northern Kazakhstan.

BACKGROUND: Previous studies of the genetic polymorphism of the Y-chromosome of Kazakhs were focussed on the Eastern, Central, Southern, and Western regions of Kazakhstan. In addition, many of these studies were limited to 17 Y-STR loci from the Yfiler. AIM: To enrich the existing Kazakhstan Y-chromosome Haplotype Reference Database from the Northern Kazakh population data by a wide set of 27 Y-STR and investigate the population genetic relationships with previously published data. SUBJECTS AND METHODS: Twenty-seven Y-STR loci from the Yfiler Plus PCR Amplification Kit were analysed in 382 healthy unrelated Kazakh males from Northern Kazakhstan. Genetic polymorphism was analysed using Arlequin software. RESULTS: A total of 326 distinct haplotypes of the 27 Y-STR loci were observed in 382 individuals. The discrimination capacity (0.9982) and haplotype diversity (0.8534) were computed. A total of 168 alleles at single-copy loci were observed and their frequencies ranged from 0.003-0.843. The pairwise genetic distance (RST) showed that the Northern Kazakh population is genetically distinct from the Chinese Kazakh population. CONCLUSIONS: Genetic polymorphism shows that the potential value of 27 Y-STR loci for forensic casework in the Northern Kazakh population and the current findings might be beneficial for paternal lineages in the study of population genetics.

[Association of leptin with anthropometric indexes, dyslipidemia and carbohydrate metabolism in Kazakh adults].

Leptin plays an important role in eating behavior, the central action of this hormone is the regulation of appetite and energy expenditure. Anthroponutritiology as a new scientific direction uses the methods of medical anthropology and nutritional science. The study of the relationship between the regulation of energy metabolism, taking into account constitutional features, and anthropometric parameters provides relevance in this direction. The purpose of the research was to study of the relationship between blood serum leptin level and body mass index (BMI) and indicators of lipid profile, carbohydrate metabolism in adult Kazakh population. Material and methods. The sample of the prospective study was 109 persons aged 18-60 years, who were divided depending on BMI into 5 groups, randomized by age and sex. We measured anthropometric parameters and biochemical parameters: serum leptin concentration, fasting blood glucose, insulin, glycated hemoglobin, HOMA-IR, lipid profile (concentration of cholesterol, low and high density lipoproteins, triglycerides, atherogenic index). Results. In the sample studied, we found that in Kazakh adults, serum leptin level correlated with BMI (ρ=0.57; p<0.01). The highest values were observed at a BMI greater than 40 kg/m2, amounting to 54.9 [33.3; 78.4] vs 10.0 [4.8; 23.1] ng/ml in overweight individuals (p=<0.005). In women, leptin levels were almost 2-fold higher than in men (24.2 vs 12.9 ng/ml, p=<0.001). No significant correlations of leptin level with age and lipid profile have been found. There was a positive association of leptin with insulin (ρ=0.28, p<0.01) and the HOMA-IR (ρ=0.21, p<0.05). Conclusion. The study showed that leptin blood level is associated with constitutional features, the highest values were found in persons with a high degree of obesity. Perhaps this result is associated with leptin resistance. Diagnostic criteria of leptin resistance are currently poorly studied. Taking into consideration clinical and specific actions of leptin there is a place for its further study as a potential biomarker of obesity.

Heterozygote of PLCE1 rs2274223 increases susceptibility to human papillomavirus infection in patients with esophageal carcinoma among the Kazakh populations.

The involvement of human papillomavirus (HPV) in the carcinogenesis of esophageal squamous carcinoma remains undetermined. However, three genome-wide association studies of esophageal cancer have identified a shared susceptibility locus at 10q23 (rs2274223: A5780G) in phospholipase C epsilon 1 (PLCE1). The current study aims to present a comprehensive and novel spectrum about the HPV genotype distribution of esophageal carcinoma in Kazakhs and assess its association with PLCE1 polymorphisms. The HPV genotypes in 183 patients with esophageal cancer and 89 controls selected from the Kazakh population were evaluated using the HPV gene chip. The PLCE1 rs2274223 variant was genotyped in esophageal carcinoma patients by MALDI-ToF Mass Spectrometry. The presence of seven HPV genotypes in esophageal carcinoma tissues-including HPV 16, 18, 35, 52, 6, 11, 43-was significantly higher at 31.7% than those in controls at 9.0% (P < 0.001). Such presence was strongly associated with increased risk of esophageal carcinoma (OR 4.70; 95% CI 2.13-10.36). Among all HPV genotypes detected, HPV16 was the most common genotype identified (29.0%, OR 4.13; 95% CI 1.87-9.13), which is significantly associated with well-differentiated esophageal carcinoma (P = 0.037). HPV-positive patients were generally younger than HPV-negative patients (70.1% vs. 29.3%, P = 0.013). PLCE1 rs2274223 genotypes AG and AG/GG were significantly associated with HPV-positive patients with esophageal carcinoma (OR 2.05, 95% CI 1.03-4.08 and OR 1.98, 95% CI 1.02-3.84, respectively). These findings suggest that heterozygote of PLCE1 rs2274223 increases susceptibility to HPV infection in patients with esophageal carcinoma among the Kazakh populations.

Associations of Amino Acids with the Risk of Prediabetes: A Case-Control Study from Kazakhstan.

BACKGROUND: The high global prevalence of prediabetes requires its early identification. Amino acids (AAs) have emerged as potential predictors of prediabetes. This study investigates the association between amino acids and prediabetes in the Kazakh population. MATERIALS AND METHODS: In this case-control study, serum AAs levels were measured using the Trace GC 1310 gas chromatography system coupled with the TSQ 8000 triple quadrupole mass spectrometer (Thermo Scientific, Austin, TX, USA) followed by silylation with the BSTFA + 1% TMCS derivatization method. Biochemical parameters, including total cholesterol, HDL-C, LDL-C, triglycerides, fasting glucose, HbA1c, and Creatinine, were assessed for each participant. Trained professionals conducted anthropometric and physical examinations (which included taking blood pressure and heart rate measurements) and family history collection. RESULTS: A total of 112 Kazakh individuals with prediabetes and 55 without prediabetes, aged 36-65 years, were included in the study. Only Alanine and valine showed a significant association with prediabetes risk among the 13 AAs analyzed. Our findings revealed an inverse relationship between Alanine and Valine and prediabetes in individuals of Kazakh ethnicity. CONCLUSION: A lower serum level of Alanine and Valine may serve as a predictive biomarker for prediabetes in the Kazakh population.

Predictive accuracy of genetic variants for eye color in a Kazakh population using the IrisPlex system.

OBJECTIVE: This study assesses the accuracy of the IrisPlex system, a genetic eye color prediction tool for forensic analysis, in the Kazakh population. The study compares previously published genotypes of 515 Kazakh individuals from varied geographical and ethnohistorical contexts with phenotypic data on their eye color, introduced for the first time in this research. RESULTS: The IrisPlex panel's effectiveness in predicting eye color in the Kazakh population was validated. It exhibited slightly lower accuracy than in Western European populations but was higher than in Siberian populations. The sensitivity was notably high for brown-eyed individuals (0.99), but further research is needed for blue and intermediate eye colors. This study establishes IrisPlex as a useful predictive tool in the Kazakh population and provides a basis for future investigations into the genetic basis of phenotypic variations in this diverse population.

Cardiac Autonomic Neuropathy Is Not Associated with Apolipoprotein E Gene Isoforms in the Kazakh Population: A Case-Control Study.

The absence of an early diagnosis of cardiac autonomic neuropathy might increase the risk of the disease, progressing to an irreversible stage. Therefore, this study aims to investigate the APOE gene isoforms in patients with cardiac autonomic neuropathy to identify early markers for predicting this disease in the Kazakh population. A total of 147 patients with cardiac neuropathy and 153 controls were examined in this case-control study. Patients were genotyped for two polymorphisms of the APOE gene using real-time PCR. Statistical calculations were performed using binary logistic regression. As a result of our study, we found that there was no statistically significant difference in the frequency of any APOE gene isoforms (APOE (ε2/ε2), APOE (ε2/ε3), APOE (ε2/ε4), APOE (ε3/ε3), or APOE (ε4/ε4)) between the patient group and the control group (p = 0.69, p = 0.64, p = 0.19, p = 0.22, p = 0.97, respectively). Thus, cardiac autonomic neuropathy is not associated with APOE gene isoforms in the Kazakh population.

Population dataset for 23 Y-STR in the Merkit clan form Kazakh population.

This study presents a comprehensive analysis of 23 Y-STR data for the Merkit clan, a subgroup within the Kerey tribe of the Kazakh people. A total of 64 complete haplotypes were generated using the PowerPlex Y23 System. The data obtained using 23 Y-STR markers has been submitted to the Y Chromosome Haplotype Reference Database (YHRD) at yhrd.org, which will significantly enhance the forensic database for the Kazakh population in Kazakhstan. The research focuses on the distribution of haplotypes within the clan and their genealogical lines, which were visualized using a Median-joining network and Multidimensional scaling plot. The study identifies four distinct haplogroup clusters, revealing important insights into the genetic makeup and historical lineage of the Merkits. This dataset not only enriches our understanding of Kazakh genetic structure but also holds significant value for anthropological and population genetic research, as well as for forensic genetics. This work bridges a notable gap in genetic research on the Merkit clan, contributing to a deeper understanding of Central Asian nomadic tribes.

Association of Genetic Markers with the Risk of Early-Onset Breast Cancer in Kazakh Women.

Breast cancer is a global health problem. It is an age-dependent disease, but cases of early-onset breast cancer (eBC) are gradually increasing. There are many unresolved questions regarding eBC risk factors, mechanisms of development and screening. Only 10% of eBC cases are due to mutations in the BRCA1/BRCA2 genes, and 90% have a more complex genetic background. This poses a significant challenge to timely cancer detection in young women and highlights the need for research and awareness. Therefore, identifying genetic risk factors for eBC is essential to solving these problems. This study represents an association analysis of 144 eBC cases and 163 control participants to identify genetic markers associated with eBC risks in Kazakh women. We performed a two-stage approach in association analysis to assess genetic predisposition to eBC. First-stage genome-wide association analysis revealed two risk intronic loci in the CHI3L2 gene (p = 5.2 × 10-6) and MGAT5 gene (p = 8.4 × 10-6). Second-stage exonic polymorphisms haplotype analysis showed significant risks for seven haplotypes (p < 9.4 × 10-4). These results point to the importance of studying medium- and low-penetrant genetic markers in their haplotype combinations for a detailed understanding of the role of detected genetic markers in eBC development and prediction.

Genotype data for 60 SNP genetic markers associated with eye, hair, skin color, ABO blood group, sex, core Y-chromosome haplogroups in Kazakh population.

OBJECTIVES: The collection of genotype data was conducted as an essential part of a pivotal research project with the goal of examining the genetic variability of skin, hair, and iris color among the Kazakh population. The data has practical application in the field of forensic DNA phenotyping (FDA). Due to the limited size of forensic databases from Central Asia (Kazakhstan), it is practically impossible to obtain an individual identification result based on forensic profiling of short tandem repeats (STRs). However, the pervasive use of the FDA necessitates validation of the currently employed set of genetic markers in a variety of global populations. No such data existed for the Kazakhs. The Phenotype Expert kit (DNA Research Center, LLC, Russia) was used for the first time in this study to collect data. DATA DESCRIPTION: The present study provides genotype data for a total of 60 SNP genetic markers, which were analyzed in a sample of 515 ethnic Kazakhs. The dataset comprises a total of 41 single nucleotide polymorphisms (SNPs) obtained from the HIrisPlex-S panel. Additionally, there are 4 SNPs specifically related to the AB0 gene, 1 marker associated with the AMELX/Y genes, and 14 SNPs corresponding to the primary haplogroups of the Y chromosome. The aforementioned data could prove valuable to researchers with an interest in investigating genetic variability and making predictions about phenotype based on eye color, hair color, skin color, AB0 blood group, gender, and biogeographic origin within the male lineage.

Determination of genetic predisposition to early breast cancer in women of Kazakh ethnicity.

Breast cancer (BC) is the most common type of cancer among women in Kazakhstan. To date, little data are available on the spectrum of genetic variation in Kazakh women with BC. We aimed to identify population-specific genetic markers associated with the risk of developing early-onset BC and test their association with clinical and prognostic factors. The study included 224 Kazakh women diagnosed with BC (≤40 age). Entire coding regions (>1700 exons) and the flanking noncoding regions of 94 cancer-associated genes were sequenced from blood DNA using MiSeq platform. We identified 38 unique pathogenic variants (PVs) in 13 different cancer-predisposing genes among 57 patients (25.4%), of which 6 variants were novel. In total, 12 of the 38 distinct PVs were detected recurrently, including BRCA1 c.5266dup, c.5278-2del, and c.2T>C, and BRCA2 c.9409dup and c.9253del that may be founder in this population. BRCA1 carriers were significantly more likely to develop triple-negative BC (OR = 6.61, 95% CI 2.44-17.91, p = 0.0002) and have family history of BC (OR = 3.17, 95% CI 1.14-8.76, p = 0.03) compared to non-carriers. This study allowed the identification of PVs specific to early-onset BC, which may be used as a foundation to develop regional expertise and diagnostic tools for early detection of BC in young Kazakh women.

Genetic markers of the risk of coronary heart disease and coronary artery thrombosis developing in the Kazakh population.

Background: Surgical methods such as coronary artery bypass grafting and percutaneous coronary interventions (PCI) are widely used along with traditional conservative therapy in the treatment of coronary artery disease. The disease outcome directly depends on timely diagnosis and treatment. A significant role in predicting the effectiveness of treatment is given to personification of treatment and management of the patient. In this case, the determining component is its individual genetic status. Methods: The study groups included persons of Kazakh nationality which identify themselves, their biological parents, and biological grandparents on the maternal and paternal side as Kazakh. Research groups included 108 people at the age from 45 to 65 years of both sexes. Blood samples genotyping was carried out by PCR using highly specific TaqMan samples. Thermo Fisher cloud application was used for genotypes determining on the base of an automatic algorithm. Results: The article presents the results of the evaluation of gene polymorphisms associated with coronary artery restenosis in a population of Kazakh nationality. 3 SNPs were determined when searching for an association with stenting due to coronary artery thrombosis: rs7543130 (p=0.009324), rs6785930 (p=0.016858), rs7819412 (p=0.061325). Conclusion: Four polymorphisms associated with the risk of developing coronary heart disease were revealed during the study of polymorphisms among the people of the Kazakh population. Three SNPs were determined when searching for an association with stenting due to coronary artery thrombosis. It should be noted that the Bonferonni correction for multiple comparisons did not reveal significant polymorphisms associated with coronary artery disease, which requires further research with more quantity of samples.

Cardiovascular Disease Prediction by Machine Learning Algorithms Based on Cytokines in Kazakhs of China.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Accurately identifying subjects at high-risk of CVD may improve CVD outcomes. We sought to systematically examine the feasibility and performance of 7 widely used machine learning (ML) algorithms in predicting CVD risks. METHODS: The final analysis included 1508 Kazakh subjects in China without CVD at baseline who completed follow-up. All subjects were randomly divided into the training set (80%) and the test set (20%). L1-penalized logistic regression (LR), support vector machine with radial basis function (SVM), decision tree (DT), random forest (RF), k-nearest neighbors (KNN), Gaussian naive Bayes (NB), and extreme gradient boosting (XGB) were employed for prediction CVD outcomes. Ten-fold cross-validation was used during model developing and hyperparameters tuning in the training set. Model performance was evaluated in the test set in light of discrimination, calibration, and clinical usefulness. RF was applied to obtain the variable importance of included variables. Twenty-two variables, including sociodemographic characteristics, medical history, cytokines, and synthetic indices, were used for model development. RESULTS: Among 1508 subjects, 203 were diagnosed with CVD over a median follow-up of 5.17 years. All 7 models had moderate to excellent discrimination (AUC ranged from 0.770 to 0.872) and were well calibrated. LR and SVM performed identically with an AUC of 0.872 (95% CI: 0.829-0.907) and 0.868 (95% CI: 0.825-0.904), respectively. LR had the lowest Brier score (0.078) and the highest sensitivity (97.1%). Decision curve analysis indicated that SVM was slightly better than LR. The inflammatory cytokines, such as hs-CRP and IL-6, were identified as strong predictors of CVD. CONCLUSION: SVM and LR can be applied to guide clinical decision-making in the Kazakh Chinese population, and further study is required to ensure their accuracies.

Combination of circulating miR-145-5p/miR-191-5p as biomarker for breast cancer detection.

BACKGROUND: Breast cancer (BC) is the most common cancer among women worldwide. At present, there is a need to search for new, accurate, reliable, minimally invasive and cheap biomarkers in addition to existing methods for the diagnosis and prognosis of BC. The main goal of this study was to test the diagnostic value of six circulating miRNAs in Kazakh women. MATERIALS AND METHODS: TaqMan-based miRNA profiling was conducted using plasma specimens from 35 BC women patients and 33 healthy women samples (control group). RESULTS: The level of all seven miRNAs (including endogenous control) normalized by synthetic cel-miR-39 were significantly elevated in the group of BC patients. Normalization using miR-222-3p as endogenous control reduced differences in level of miRNAs between groups; as a result, only three miRNAs were significantly upregulated in the group of BC patients-miR-145-5p (P = 6.5e-12), miR-191-5p (P = 3.7e-10) and miR-21-5p (P = 0.0034). Moreover, ROC analysis showed that the use of miR-145-5p and miR-191-5p, both individually (AUC = 0.931 and 0.904, respectively) or in combination (AUC = 0.984), allows to accurately differentiate BC patients from healthy individuals. CONCLUSIONS: Two plasma miRNAs-miR-145-5p and miR-191-5p-are potential biomarkers for diagnosis of BC in the Kazakh population. The findings need to be further substantiated using a more representative sample.

Relationship between esophageal cancer-related gene 2 polymorphism and esophageal squamous cell carcinomas in Kazakhs and Hans of Xinjiang.

In recent years, many studies have focused on the novel esophageal cancer-related gene 2 (ECRG2), which might be important in esophageal cancer development. The aim of this study is to investigate the relationship between ECRG2 short tandem repeat (STR) polymorphism and susceptibility to esophageal squamous cell carcinomas (ESCCs) in Kazakhs and Hans in Xinjiang. ECRG2 genotypes were detected by PCR-SSCP in 178 cases of esophageal carcinomas and 153 blood samples from the Kazakh and Han population. In Kazakhs and Hans, the frequencies of ECRG2 STR genotypes TCA3/TCA3, TCA4/TCA4, and TCA3/TCA4 were 47.8%/8.7%, 43.5%/67.9%, and 7.1%/25.0% in esophageal carcinomas with metastasis, respectively; and 14.1%/38%, 47.9%/14.3%, and 44.6%/41.1% in carcinomas without metastasis, respectively. A significant difference was observed between the groups with metastasis and without metastasis (Kazakh: χ2=13.77, P<0.01; Han: χ2=26.183, P<0.01). Compared with patients who carried the TCA4/TCA4 genotype, those who carried the TCA3/TCA3 genotype were at an increased risk of ESCC, with the adjusted odds ratios being 4.06 (95% confidence interval (CI), 1.69-9.74) in Kazakhs and 3.25 (95% CI, 1.25-8.45) in Hans. Our findings suggested that subjects who carried the TCA3/TCA3 genotype are at an increased risk of ESCC and metastasis compared with those who carried the TCA4/TCA4 genotype.

Type 2 diabetes mellitus: distribution of genetic markers in Kazakh population.

BACKGROUND: Ethnic differences exist in the frequencies of genetic variations that contribute to the risk of common disease. This study aimed to analyse the distribution of several genes, previously associated with susceptibility to type 2 diabetes and obesity-related phenotypes, in a Kazakh population. METHODS: A total of 966 individuals belonging to the Kazakh ethnicity were recruited from an outpatient clinic. We genotyped 41 common single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes in other ethnic groups and 31 of these were in Hardy-Weinberg equilibrium. The obtained allele frequencies were further compared to publicly available data from other ethnic populations. Allele frequencies for other (compared) populations were pooled from the haplotype map (HapMap) database. Principal component analysis (PCA), cluster analysis, and multidimensional scaling (MDS) were used for the analysis of genetic relationship between the populations. RESULTS: Comparative analysis of allele frequencies of the studied SNPs showed significant differentiation among the studied populations. The Kazakh population was grouped with Asian populations according to the cluster analysis and with the Caucasian populations according to PCA. According to MDS, results of the current study show that the Kazakh population holds an intermediate position between Caucasian and Asian populations. CONCLUSION: A high percentage of population differentiation was observed between Kazakh and world populations. The Kazakh population was clustered with Caucasian populations, and this result may indicate a significant Caucasian component in the Kazakh gene pool.