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.

The effect of AGTR1, AGТ, LPL, ADRB2 gene polymorphisms on central obesity in adolescents of the Kazakh population.

BACKGROUND: Abdominal obesity, usually measured by waist circumference and waist-to-hip ratio, is more closely related to metabolic dysfunctions that are associated with cardiovascular diseases than general obesity, which is usually assessed by body mass index. The purpose of our study was to study the distribution of alleles and genotypes AGTR1, AGТ, LPL and ADRB2 among adolescents of the Kazakh population and to identify the relationship of these genes with predictors of obesity. METHODS: The study involved 184 adolescents aged 15-18 years of the Kazakh population. RESULTS: As a result of the study, it was revealed that the G allele of the rs328 polymorphism of the LPL gene reduces the risk of developing abdominal obesity compared to the C allele.The C/G genotype reduces the risk of developing abdominal obesity. We have identified among the studied adolescents of the Kazakh population an increase in the ratio of waist volume (WV) to hip volume (HV) among boys, which may in the future lead to obesity and cardiovascular diseases in general. CONCLUSION: It was also found that the G allele of the rs328 polymorphism of the LPL gene reduces the risk of abdominal obesity. Therefore, in addition to determining BMI, we recommend determining the ratio WV to HP. It was found that an increase in the ratio of WV/HV by 1 cm increases the chance of developing hypoapolipoproteinemia A1 (Tab. 4, Fig. 1, Ref. 23). Text in PDF www.elis.sk Keywords: obesity, body mass index, waist-to-hip ratio, AGTR1, AGТ, LPL, ADRB2.

The Study of the Outbreak of Coronavirus Infection in a General Hospital in Almaty.

The study aimed to identify the possible causes of COVID-19 outbreak and its development in a general hospital in Almaty (from April 11 to May 6, 2020), where 682 persons were identified with a COVID-19. 546 were hospital employees (48.9%), including doctors (57.8%), nurses (53.4%), junior medical personnel (54.4%) and other personnel (23.3%), and also among 136 patients. The attack rate among women was 50.0%, and incidence rate was higher amongst young employees < 30 years old (57.0%). The analysis showed that there was a failure of the management of the medical personnel in such critical situation.

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.

Internal exposure to neutron-activated 56Mn dioxide powder in Wistar rats-Part 2: pathological effects.

To fully understand the radiation effects of the atomic bombing of Hiroshima and Nagasaki among the survivors, radiation from neutron-induced radioisotopes in soil and other materials should be considered in addition to the initial radiation directly received from the bombs. This might be important for evaluating the radiation risks to the people who moved to these cities soon after the detonations and probably inhaled activated radioactive "dust." Manganese-56 is known to be one of the dominant radioisotopes produced in soil by neutrons. Due to its short physical half-life, 56Mn emits residual radiation during the first hours after explosion. Hence, the biological effects of internal exposure of Wistar rats to 56Mn were investigated in the present study. MnO2 powder was activated by a neutron beam to produce radioactive 56Mn. Rats were divided into four groups: those exposed to 56Mn, to non-radioactive Mn, to 60Co γ rays (2 Gy, whole body), and those not exposed to any additional radiation (control). On days 3, 14, and 60 after exposure, the animals were killed and major organs were dissected and subjected to histopathological analysis. As described in more detail by an accompanying publication, the highest internal radiation dose was observed in the digestive system of the rats, followed by the lungs. It was found that the number of mitotic cells increased in the small intestine on day 3 after 56Mn and 60Co exposure, and this change persisted only in 56Mn-exposed animals. Lung tissue was severely damaged only by exposure to 56Mn, despite a rather low radiation dose (less than 0.1 Gy). These data suggest that internal exposure to 56Mn has a significant biological impact on the lungs and small intestine.