Dynamics of body weight during lifestyle modification in patients with high cardiovascular risk, depending on the carriage of various variants of thrifty genes

Objective — to study the relationship between the carriage of polymorphic variants PPARG2 (Pro12Ala), ADRB2 (Gln27Glu), ADRB2 (Agr16Gly), ADRB3 (Trp64Agr), FABP2 (Thr54Ala) and changes in anthropometric parameters under the influence of increased physical activity in individuals with high cardiovascular risk. Materials and methods. In total, 205 people were examined during the period of years 2019 — 2021. Patients were advised to use physical activity frequently in the form of regular exercises. Among patients who passed the 2nd observation point, 60.5 % (124 patients) reported that they expanded their physical activity, 39.5 % (81 patients) began regular exercises. The study included patients with high cardiovascular risk. The International Physical Activity Questionnaire (IPAQ) was used to assess physical activity. Assessments included anthropometric parameters (weight, height, body mass index, waist and hip circumference, body composition (Composition Monitor BF511, Omron, China, 2015)), levels of total cholesterol, triglycerides, low‑density lipoproteins. Muscle strength (kg/cm2) was assessed using an electric dynamometer on the wrist Camry EH101 2013 (2018). Isolation and purification of DNA from the whole blood was carried out using a set of reagents «DNA‑sorb‑B» (Amplisens, RF) according to the manufacturer’s instructions. Amplification of DNA and genotyping at polymorphic sites in the genes PPARG2, ADRB2, ADRB3, FABP2 was performed by real‑time PCR using a set of reagents «SNP‑EXPRESS‑SHOT» («Litech», RF) according to the manufacturer’s instructions using the product detection system real‑time CFX96 Touch (BioRad Laboratories Pte.Ltd.). Results. Depending on the changes in anthropometric parameters, patients were divided into 2 subgroups: in subgroup 1 there was no decrease in BMI before 30.69 ± 7.25 kg/m2, after 29.03 ± 6.84 kg/m2; p = 0.436, and in subgroup 2 a significant decrease in BMI before 31.85 ± 3.68 kg/m2, after 26.79 ± 3.91 kg/m2; p = 0.041. It was revealed that the decrease in BMI in subgroup 2 was accompanied by a statistically significant decrease in the proportion of adipose tissue (р = 0.011) and an increase the proportion of muscle tissue (р = 0.030). In both groups, blood pressure significantly decreased. Heart rate (HR) decreased in both groups, but these changes did not reach statistical significance (p = 0.43). Changes in anthropometric parameters were not accompanied by significant changes in total cholesterol, LDL cholesterol, triglycerides levels. A significant increase in HDL cholesterol levels was revealed. It was found that patients with CC and GG variants of the polymorphic locus PPARG2 (Pro12Ala), CG and GG variants of the polymorphic locus ADRB2 (Gln27Glu) and TT variant of the polymorphic locus ADRB3 (Trp64Agr) prevailed in group 2. No significant differences were found for the FABP2 locus (Thr54Ala). In subgroup 1, there were no significant differences in people with various polymorphic variants of genes. Conclusions. Associations have been established between the carriage of CG/CG + GG PPARG2 (rs1801282), AA/AA + AG ADRB2 (rs1042713) and TT ADRB3 (rs4994) and a decrease in body mass index during exercise expansion in individuals with high cardiovascular risk.

Study of the FUT2 gene association with infection and clinical manifestations of Helicobacter pylori infection

The aim of the pilot study of a group of adolescents with H. pylori infection was to study the preliminary data obtained on the rs602662 locus of the FUT2 gene and to establish its role in the realization of clinical manifestations of chronic gastritis, gastric ulcer and duodenal ulcer associated with H. pylori.Methods: The study included 91 patients. The study for the presence of the polymorphic locus rs602662 of the FUT2 gene was carried out by the standard TaqMan PCR method on a Real-Time CFX96 Touch amplifier. The duration of the study was 6 months.Results: The main group included 25 adolescents aged 16 to 17 years 11 months, the control group included 20 patients. Patients infected with H. pylori more often noticed symptoms of dyspepsia - in 36%, compared with the control group - 9.7%. The presence of a family history in the main group for associated diseases had a significant difference, χ2 = 4.97, p <0.05.To assess the contribution of the genotype of the rs602662 locus of the FUT2 gene to the risk of clinical manifestations in H. pylori infection, the main group was divided into subgroups. In the distribution of alleles in these groups, statistically significant differences were revealed.Allele “A” has a protective effect against the onset of clinical symptoms of dyspepsia. The odds ratio (OR) with the carriage of allele “A” (genotypes A / A and G / A versus G / G) to have clinical symptoms with a positive H. pylori status was 0.175 (CI = [0.049-0.625] chi2 = 7.79 p = 0.0053).Conclusion. As a result of the study, we were unable to identify a significant association of alleles and genotypes of the rs602662 locus of the FUT2 gene with clinical manifestations of H. pylori infection. At the same time, carriers of the A allele have a pronounced association with the absence of clinical symptoms in patients with a positive H. pylori infection status of 0.175 (C.I. = [0.049-0.625] chi2 = 7.79 p = 0.0053).

Associations of molecular genetic predictors of type 2 diabetes mellitus with hyperglycemia in extremely low birth weight infants

Hyperglycemia in premature newborns is an independent risk factor for death, so blood glucose testing is widely used in the practice of neonatal intensive care units.Objective: to evaluate the associations of the frequency of carriage of allelic variants of polymorphic loci of genes predisposing to type 2 diabetes mellitus in newborns with extremely low body weight and hyperglycemia.Methods. The study design is prospective, controlled, single – center, non-randomized. Genomic DNA samples were studied in newborn infants with extremely low body weight (ELBW) (n = 105). Previously, we compared the distribution of allele frequencies of the studied genes between a group of newborns with ELBW and a population sample of adults (control). Then, the distribution of allele frequencies of the genes was compared depending on the presence of hyperglycemia in newborns with ELBW. For the analysis, loci with already known association with the development of type 2 diabetes mellitus were selected ‒ ADRB2 (rs1042713) and (rs1042714), ADRB3 (rs4994), GNB3 (rs5443), PPARA (rs4253778), PPARD (rs2016520), TCF7L2_IVS3 (rs7903146) and TCF7L2_IVS4 (rs12255372), PPARGC1A (rs8192678), MTHFR (rs1801131), PPARG (rs1801282), MTNR1B (rs10830963), SIRT1 (rs7069102).Results. In newborns with ELBW, we found a more frequent occurrence of the mutant allele A of the polymorphic locus rs8192678 in the PPARGC1A gene and the allele C of the polymorphic locus rs4253778 in the PPARA gene, in contrast to the adult population sample. But in newborns with ELBW, hyperglycemia is most likely associated with the carrier of the allele C rs1801282 of the PPARG gene (χ2 = 18.972, p < 0.001) and the allele T rs7903146 in the TCF7L2 gene (χ2 = 11.496, p < 0.001).Conclusions. The carriage of the allele С rs1801282 of the PPARG gene is characterized by the presence of a strong conjugation with hyperglycemia in newborns with extremely low body weight. It is desirable to monitor the level of glycemia in the conditions of neonatal intensive care units, taking into account the carriage of genes predisposing to hyperglycemia.

The genetic potential of Taxus sumatrana medicinal plants in Kerinci Regency

Taxus -a taxol-producing medicinal plant that mostly found in highland area- is a species in genus Taxus and family Taxaceae. This study was aimed to determine the genetic diversity within and between population of T. sumatrana in Kerinci Regency, i.e. Mount Kerinci and Mount Tujuh, based on altitude. The genetic diversity was analyzed with RAPD analysis. The altitude was categorized as low (<2000 m asl) and high (>2000 m asl). The cambium extraction was carried out based on CTAB method. DNA amplification was conducted in RAPD method on machine of PCR System 9700 Applied Biosystems. Nine RAPD primers were used in this study. The results revealed that the average of polymorphic locus was 53.89%. Genetic diversity within population was fairly high with value of 0.1799 and Shannon index of 0.2746. Among the four populations, the population of High Tujuh showed the highest level of variability (He=0.2044). The Nei genetic distance between populations was ranging from 0.0567 to 0.1302. The potential of High Tujuh population is still large enough so that it can still be explored for genetic conservation and cultivated as a taxol-producing material which is useful for medicine.

Genetic diversity of Kemerovo pig breed based on microsatellite markers

Today, the urgent task is to preserve the gene pool of local and regional breeds with their special and useful traits. These features allow them to represent an additional reservoir of genetic diversity. Analysis of the genetic diversity of three pig populations (Kemerovo pig breed, Kemerovo × Landrace crossbreds and Kemerovo × Landrace × Pietrain crossbreds) by microsatellites showed that significant allelic diversity is observed for some loci, while for others it is low. The highest number of alleles was in the purebred pigs in comparison with crossbreds. The greatest range of alleles per locus was noted in the three-breed cross pigs. The most polymorphic locus in all populations was SO005, and the least polymorphic was SW72. It was noted that for most loci the observed heterozygosity corresponds to the expected one, while for others a shortage of heterozygotes is detected.

Milk consumption and gastrointestinal symptoms in preschool girls with different lactase genotypes

AIM: To analyze the frequency of milk consumption and subjective symptoms of intolerance to dairy products in the population of three- to six-year-old girls (born and resident in Samara) based on the genotype of the lactase gene. MATERIALS AND METHODS: We included 103 preschool girls ranging three to six years of age. Parents were questioned about the frequency of milk consumption by the child (per week), as well as the presence of gastrointestinal symptoms in their children (abdominal pain, bloating, flatulence and diarrhea) and the suspected association of symptoms with milk consumption (according to the parents). Buccal samples were taken from all girls to determine the polymorphism of the lactase genes (determination of C/T-13910 variant of the MCM6 gene). RESULTS: A significant relationship between the frequency of milk consumption and the variant of the polymorphic locus of the lactase gene, MCM6 [C 13910T; which affects the expression of the lactase gene (LCT)] has not been established. There is no correlation in the enlarged gradation of frequent milk consumption (47 times a week) and rare milk consumption (23 times a week or less): of 53 girls with the CC genotype 27 (51%) often drink milk, 26 (49%) rarely drink milk; of 39 girls with CT genotype 23 (59%) often consume milk, 16 (41%) rarely consume milk; of 11 girls with the TT genotype, 8 (73%) often consume milk, 3 (27%) rarely consume milk (c2 1.94, p = 0.379). There was no significant relationship between the frequency of milk consumption, subjective symptoms of lactose intolerance (abdominal pain, bloating, flatulence and diarrhea) and the genotype; these symptoms were found only in four girls carrying the C allele (CC and CT genotypes) though not detected in girls with TT genotype. CONCLUSION: In girls of 36 years old, there is no relationship between the frequency of milk consumption, subjective symptoms of lactose intolerance and genotype of lactase gene.

Allele frequency divergence reveals ubiquitous influence of positive selection in Drosophila

Resolving the role of natural selection is a basic objective of evolutionary biology. It is generally difficult to detect the influence of selection because ubiquitous non-selective stochastic change in allele frequencies (genetic drift) degrades evidence of selection. As a result, selection scans typically only identify genomic regions that have undergone episodes of intense selection. Yet it seems likely such episodes are the exception; the norm is more likely to involve subtle, concurrent selective changes at a large number of loci. We develop a new theoretical approach that uncovers a previously undocumented genome-wide signature of selection in the collective divergence of allele frequencies over time. Applying our approach to temporally resolved allele frequency measurements from laboratory and wild Drosophila populations, we quantify the selective contribution to allele frequency divergence and find that selection has substantial effects on much of the genome. We further quantify the magnitude of the total selection coefficient (a measure of the combined effects of direct and linked selection) at a typical polymorphic locus, and find this to be large (of order 1%) even though most mutations are not directly under selection. We find that selective allele frequency divergence is substantially elevated at intermediate allele frequencies, which we argue is most parsimoniously explained by positive—not negative—selection. Thus, in these populations most mutations are far from evolving neutrally in the short term (tens of generations), including mutations with neutral fitness effects, and the result cannot be explained simply as an ongoing purging of deleterious mutations.

Clinical and genetic factors associated with the risk of recurrent ischemic events in patients with stable stenocardia

The aim of the study was to assess the clinical and genetic factors associated with the risk of recurrent ischemic events in patients with stable stenocardia (SS). Materials and methods. A total of 100 patients with SS were examined and followed-up for 15.3±8.3 months. The patients were divided into subgroups (SG): SG1 (n=51) – persons without events, SG2 (n=49) persons with recurrent ischemic events (hospitalization due to the development of pain syndrome, re-stenting due to stent restenosis, myocardial infarction, cerebral infarction and death from cardiovascular causes), SGB (n=11) – persons with «major» recurrent ischemic events (re-stenting due to stent restenosis, myocardial infarction, cerebral infarction and death from cardiovascular causes) , SGG (n=89) – persons without «major» events. The obtained survey data (general clinical, aggregometry, polymor phism of genes of platelet fibrinogen receptor ITGB3 (T1565C), platelet collagen receptor ITGA2 (C807T), ADP platelet receptor P2RY12, H1/H2 (T744C)) were analyzed using the STATISTICA 10.0 software. Results. In SG2, men predominated (χ2 =9.2; p<0.01), past MI was more common (χ2 =4.8; p<0.05), more stents were implanted (2.4±1.9 versus 1.7±1.1, p<0.05), TRAP-test values were higher (p<0.05) compared to SG1. In SGB, greater number of stents were implanted (3.1±2.2 versus 1.61±1.57, p<0.05), the carriage of the TC genotype of the ITGB3 gene was more common, (p<0.05), a combination of gene mutations ITGB3 and P2RY12 was more common, (p<0.05) compared to SGG. A logistic regression equation was constructed, including the presence of diabetes mellitus, the number of platelets in the blood test, the ASPI-test values, the carriage of the 1565C allele of the ITGB3 gene, the number of stents implanted, which makes it possible to determine the likelihood of developing «major» recurrent ischemic events with a cut-off threshold LP₀=0.0965, with sensitivity – 81.82 %, specificity – 78.48 %, overall accuracy – 78.89 %. Conclusions. The factors associated with the development of recurrent ischemic events are: male sex, previous MI, a greater number of implanted stents, and high TRAP-test values. The factors associated with the development of recurrent «major» ischemic events are: a greater number of implanted stents, carriage of the TC genotype of the ITGB3 gene, carriage of a combination of mutations of the H1/H2 polymorphic locus of the P2RY12 gene and the T1565C polymorphic locus of the ITGB3 gene, diabetes mellitus, the number of platelets in blood test, ASPI-test values.

Association of SCN5A gene polymorphism with dilated cardiomyopathy

Subjects and methods. The study included patients with IDC (group 1; n=111, 89.2% men, average age 51.7±9.7 years) and ICM (group 2; n=110, 91.5% men, average age 58.7±8.4 years). All patients (IDC and ICM) underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the group 1. And those patients who were reliably diagnosed with coronary artery disease were in the group 2, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. The control group (n=121, average age 53.6±4.8 years) included patients who had no manifestations of cardiovascular diseases. The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A/G polymorphism of the SCN5A gene (rs1805124).Results. In the group with IDC 51.4% of patients were carriers of the common homozygous AA genotype, the heterozygous AG genotype-40.5%, and the rare homozygous GG genotype-8.1%. In the control group 63.3% of patients were identified as carriers of a homozygous genotype by a common allele, and 33.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 3.2%. The analysis revealed a statistically significant decrease in the frequency of carrying the homozygous AA genotype in patients with IDC compared to the control group of the rs1805124 polymorphism of the SCN5A gene. In the group of patients with ICM, the А allele (69.5% vs. 80.1%, p=0.003) and the AA genotype (50.9% vs. 63.3%, p=0.030) were significantly less common than in the control group. The rare homozygous GG genotype was statically more common in patients with ICM compared to the control group (11.8% vs. 3.2%, p=0.004). Also, the G allele in the group of patients with ICM was detected statically significantly more often than in the control group (30.5% vs. 19.9%, p= 0.003).Conclusion. The polymorphic locus rs1805124 of the SCN5A gene is associated with both IDC and ICM. Homozygous genotype AA and allele A are conditionally protective factors for the development of these conditions in men.