Genetic regulation of testosterone level in overweight males from the Kazakh population and its association with hypogonadism.

Male hypogonadism and erectile dysfunction in different populations are associated with excess body weight. A key aspect in most studies is the metabolism of sexual hormones, primarily testosterone. At the same time, the binding protein sex hormone binding globulin (SHBG) can play a large role, as it determines the ratio of total and bioavailable testosterone in blood, i.e. both the hormone content and level of its production. Recent research has identified common mutations that affect SHBG levels, such as the rs727428 polymorphic locus, which is associated with alterations in histone protein function, affecting the regulation of ribonucleic acid (RNA) protein SHBG synthesis. Similar relationships have been observed for prevalent mutations, including rs5934505 and rs10822184, in diverse populations. This study involved 300 individuals of Kazakh nationality from the Eastern Kazakhstan region, examining three polymorphic variants of the SHBG gene (rs727428, rs5934505, and rs10822184). The participants were categorized into three groups: individuals with hypogonadism and obesity (group 1, n=85), those with excess body weight but no hypogonadism (group 2, n=70), and individuals with neither excess body weight nor hypogonadism (group 3, n=145). The frequency of mutant gene alleles impacting GPS (SHBG) synthesis in the Kazakh population was notably high, comparable to European and South-East Asian populations. However, the association between excess body weight and these mutations exhibited varying patterns. Hypogonadism was linked to decreased GPS levels, strongly correlating with total testosterone but not bioavailable testosterone. The retention of sexual functions in overweight men was not always directly related to BMI levels and GPS concentrations.

Biomarkers of immunothrombosis and polymorphisms of IL2, IL6, and IL10 genes as predictors of the severity of COVID-19 in a Kazakh population.

OBJECTIVES: To study the role of biological markers of immunothrombosis and polymorphisms of cytokine genes IL2, IL6, IL10 and their influence on the severity of COVID-19 in a Kazakh population. METHODS: A total of 301 patients of Kazakh nationality with a confirmed diagnosis of COVID-19 participated in the retrospective study, including 142 patients with severe and 159 with a mild course. Single nucleotide polymorphisms IL2R rs1801274, IL6 rs2069840, and IL10 rs1800872 were genotyped by real-time PCR. Activated partial thromboplastin time, normalized ratio, prothrombin index, prothrombin time, fibrinogen prothrombin time, fibrinogen, D-dimer, and C-reactive protein analysis were also conducted. RESULTS: The average age of patients with severe COVID-19 is higher than of patients with mild COVID-19 (p = 0.03). The findings showed that fibrinogen, D-dimer, and C-reactive protein were significantly greater in the group of patients with severe COVID-19 (p = 0.0001). A very strong correlation between the severity of COVID-19 with the D-dimer and C-reactive protein (p = 0.9) (p = 0.02) was found. CONCLUSION: The results of our study confirm that D-dimer, fibrinogen, and CRP are biomarkers of inflammation and hypercoagulation that serve as predictors of immunothrombosis affecting the severity of COVID-19. D-dimer is also associated with IL10 rs1800872 gene polymorphism in the Kazakh population with severe COVID-19.

Association of lipid parameters with insulin resistance in the Kazakh population.

BACKGROUND: Insulin resistance (IR) is a consequence of chronic adipose tissue inflammation and underlies the pathogenesis of several diseases, such as type 2 diabetes mellitus, cardiovascular diseases and metabolic syndrome. In this study, we examined the association between dyslipidaemia and IR; directly comparing conventional lipid ratios and apoB/apoA1 ratios for strength and independence as risk factors for IR in a Kazakh population. METHODS: The design of this study was a case-control study. There were 507 participants in the study. We examined each participant's plasma total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, apolipoprotein B, and apolipoprotein A1. IR was determined using an IR homeostasis model assessment (HOMA-IR). To assess the risk of an atherogenic blood lipid profile, atherogenicity coefficients were calculated: Bad cholesterol to good cholesterol ratio ((TC-HDL)/HDL); TG to HDL ratio (TRG/HDL); apoB to apoA1 ratio (apoB/apoA1). RESULTS: In this study, high waist circumference and BMI were more common in men. The group with IR had significantly higher waist circumference (cm) (p = 0.0001) and BMI (kg/m2) (p = 0.04) than the group without IR. The risk of IR was significantly associated with the apoB/apoA1 ratio (p = 0.03). Analysis of the association between HOMA-IR and apoB/apoA1 ratio increased the risk of IR at apoB/apoA1 ratios of 0.71 to 0.85 and above 0.86 by a factor of 1.93 and 1.84, respectively. HOMA-IR levels were weakly significantly correlated with TG levels (rS = 0.3; p = 0.0001) and very weakly positively correlated with apoB levels (rS = 0.1; p = 0.002) and apoB/apoA1 (rS = 0.1; p = 0.001), there was a weak negative correlation with apoA1 levels (rS = -0.1; p = 0.02). Logistic regression analysis showed that the risk of developing IR was significantly lower in men than in women, adjusted OR (95% CI) = 0.75 (0.49-1.0) p = 0.02. CONCLUSION: In our study, IR was more common in Kazakh women than in Kazakh men. IR was also associated with apoB and TG levels. Thus, we suggest that analysis of TG, apoB and apoB/apoA1 ratio may be recommended as early predictors of IR risk in the Kazakh population (Tab. 3, Ref. 22). Text in PDF www.elis.sk Keywords: insulin resistance, dyslipidaemia, apolipoproteins, triglycerides, lipids.

Associations between serum levels of brain-derived neurotrophic factor, corticotropin releasing hormone and mental distress in vitiligo patients.

Vitiligo is clinically characterized by the appearance of non-symptomatic depigmented macules, but the disorder is highly correlated with a wide range of psychiatric disorders and psychological problems. The aim of our study was to investigate serum brain-derived neurotrophic factor (BDNF) and corticotropin releasing hormone (CRH) levels in vitiligo patients and healthy controls in relation to the observed symptoms of depression and anxiety disorders. This study comprised 96 vitiligo patients and 96 healthy controls who filled out the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales. Serum levels of BDNF and CRH were measured using enzyme-linked immunosorbent assay (ELISA) technique. There was a significant increase of depression and anxiety scores in vitiligo patients as compared with healthy controls (P < 0.05). The serum levels of BDNF were significantly lower in vitiligo patients than in healthy individuals (Z = 4.002; P < 0.001), while the serum levels of CRH were markedly higher in cases than those in controls (Z = 3.764; P < 0.001). The significant positive correlations between serum CRH levels and GAD-7, PHQ-9 scores were observed. However, the aforementioned psychometric scales did not correlate significantly with serum BDNF level. Vitiligo is associated with the depression and is closely linked with lower BDNF levels.

Association of polymorphism genes LPL , ADRB2 , AGT and AGTR1 with risk of hyperinsulinism and insulin resistance in the Kazakh population.

Hyperinsulinism and insulin resistance are closely associated with several common diseases including type 2 of diabetes, cardiovascular diseases, and metabolic syndrome. The present study aimed to determine the association between hyperinsulinism, insulin resistance and the polymorphism of genes, including angiotensin II receptor type 1 (AGTR1), angiotensinogen (AGT), ß2-adrenoreceptor (ADRB2) and lipoprotein lipase (LPL), in the Kazakh population. The design of the current research was a case-control study, involving 460 subjects (age range, 18-65 years). For every subject, plasma glucose, insulin, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, apolipoprotein B and apolipoprotein A1 were examined. Moreover, reverse transcription-quantitative PCR was conducted to detect the polymorphism genes LPL Ser447Ter, ADRB2 Gln27Glu, AGT Thr174Met and AGTR1 A1166C. Hyperinsulinism was considered when the insulin level was elevated >24.9 IU/ml. The homeostasis model assessment insulin resistance (HOMA-IR) was used to evaluate insulin resistance. The subjects were divided into hyperinsulinism (17 men and 24 women) and normal level insulin (214 men and 205 women) groups, which were also split into insulin resistance group (HOMA-IR >2.7; 80 men and 105 women) and those without insulin resistance group (151 men and 124 women). The results suggested that LPL Ser447Ter (rs328) allele G was associated with a lower risk of hyperinsulinism (P=0.037). Furthermore, polymorphisms of genes ADRB2 Gln27Glu (rs1042714), AGT Thr174Met (rs4762) and AGTR1 A1166C (rs5186) were not associated with hyperinsulinism and insulin resistance in the Kazakh population. No interaction was identified between LPL Ser447Ter, ADRB2 Gln27Glu, AGT Thr174Met and AGTR1 A1166C. Therefore, the results indicated that haplotype combinations were not associated with insulin resistance.

Association of radiation risk in the second and third generations with polymorphisms in the genes CYP1A1, CYP2E1, GSTP1 and changes in the thyroid.

BACKGROUND: To study the association of radiation risk in the 2nd -3rd generations with polymorphisms in the genes CYP1A1, CYP2E1, GSTP1 and changes in the thyroid. METHODS: 5 polymorphic gene variants (rs1048943, rs4646421, rs2070676, rs3813867, rs1695) were studied in 399 people living in the East Kazakhstan region in this research. 248 people of the 2nd - 3rd generation lived in the territory with radiation exposure in Abai, Borodulikha areas, and 151 people the comparison group lived in Kurchum district without radiation exposure comparable in sex and age with control group. RESULTS: The results show that there is a significant association of rs1048943 in exposed and unexposed groups (p < 0.003), and the absence of association of rs4646421, rs2070676, rs3813867, rs1695 in the studied groups. The mean value of thyroxine in carriers of the AG + GG genotype of rs4646421 is significantly lower than in AA genotype carriers (p = 0.04); no significant changes were found in genotypes' distribution with thyroid-stimulating hormone and anti-thyroid peroxidase indicators. Significant changes were in levels of anti-thyroid peroxidase between exposed and unexposed groups (p = 0.007). The thyroxine - thyroid-stimulating hormone levels were not significantly different in exposed and unexposed groups (p > 0.3). CONCLUSIONS: This study demonstrated the association of rs1048943 polymorphism with living in the radiation zone in the 2nd and 3rd generations for the first time. Thyroxine levels decrease was identified in the 2nd and 3rd generation residents of the exposed area, as well as a significant increase of anti-thyroid peroxidase occurs in individuals of the 2nd and 3rd generation living in areas with radiation exposure.

BRCA1 and TP53 Gene-Mutations: Family Predisposition and Radioecological Risk of Developing Breast Cancer.

Frequencies of polymorphisms of genes BRCA1 and TP53 in breast cancer (BC) patients with a BC family history and radiation history were assessed and compared in the Semey region of Kazakhstan. The study included 60 women directly irradiated by the activities of the Semipalatinsk test site with a calculated effective equivalent dose of 500 mSv and their first generation descendants (group BC+Her+Exp); 65 women with family BC and absence of radiological history - the effective equivalent dose due to anthropogenic sources not exceeding 50 mSv (group BC+Her-Exp). The comparison group consisted of 65 women patients with breast cancer without family and radiological history (BC-Her-Exp). The control group comprised 60 women without breast cancer and without family and radiological history (nonBC). We carried out the genotyping of the polymorphisms c.2311T>C, c.4308T>C and 5382insC of the BRCA1 gene and rs1042522 of the TP53 gene. The frequency of the polymorphism c.2311T>C was significantly higher in patients of the group BC+Her+Exp than in healthy women, and of the polymorphism 5382insC in BC+Her+Exp compared to all other groups. The frequency of the rs1042522 polymorphism of TP53 was significantly higher in all groups of patients with breast cancer compared with the control group. Differences between groups of women with breast cancer were significant only in BC+Her+Exp vs. BC+Her-Exp. Combinations of polymorphisms of the genes BRCA1 and TP53 predominated in women with a family and radiological history.

IL17A gene polymorphisms: relationship to predisposition for chronic viral hepatitis and progression to liver cirrhosis in kazakh population.

Introduction: This work is the first genetic association study of a potential relationship of single nucleotide polymorphisms rs8193036 and rs2275913 located in the IL17A promoter on chromosome 6p12 to chronic viral hepatitis and its progression in Kazakh population. Purpose: Evaluation of the effect of IL17A polymorphism on predisposition for chronic hepatitis B and C and its progression to liver cirrhosis. Materials and Methods: A total of 862 individuals were enrolled in the retrospective case-control association study. Among the participants, 100 patients had chronic hepatitis B and/or C and liver cirrhosis, and 341 patients had chronic viral hepatitis only. Four hundred twenty-one (421) healthy HBV- and HCV-negative donors without liver diseases were recruited as population control. single nucleotide polymorphisms rs8193036[T/C] and rs2275913[G/A] were genotyped by TaqMan assays using genomic DNA extracted from peripheral blood cells. Results. Minor allele frequencies of rs8193036[C] and rs2275913[A] in the groups of patients were very similar to those observed in the control population, 0.4 and 0.3, respectively. Multivariate logistic regression analysis revealed odds ratios close to 1.0 and confidence intervals overlapping with the value of 1.0 and statistical significance p > 0.4 for any groups under comparison in the multiplicative model of inheritance. conclusion: No significant association between two single nucleotide polymorphisms, rs8193036 and rs2275913 in the IL17A promoter, and susceptibility to chronic viral hepatitis C and/or B and disease progression to liver cirrhosis in Kazakh population were found.