The Effect of Polymorphisms of Energy Metabolism Genes on Metabolic Disorders in Overweight Adolescents of Two Ethnicities.

The aim of this cross-sectional observational study is to determine the contribution of polymorphisms of energy metabolism genes into metabolic disorders in Russian and Buryat adolescents with overweight and obesity. The study included 354 Russian and Buryat adolescents aged 13-18 years. Body mass index and serum levels of glucose, insulin, and leptin were measured and insulin resistance index HOMA-IR was calculated. Molecular genetic analysis for the presence of 9 loci of energy metabolism genes LEP, LEPR, POMC, FTO, and MC4R were analyzed. It was found that the risk of metabolic disorders is associated with the presence of polymorphic loci of leptin receptor gene LEPR and melanocortin receptor gene MC4R (LEPR rs1137100+LEPR rs1137101 and LEPR rs1137100+MC4R rs17782313) in Russian adolescents with overweight and obesity and polymorphisms of the gene FTO (FTO rs9939609+rs8050136) associated with fat mass and obesity in Buryat adolescents.

Serum Serotonin as a Biomarker of the Efficacy of PAP-Therapy in Sleep Apnea Syndrome.

Serum serotonin levels were determined by HPLC in 30 patients with diagnosed obstructive sleep apnea syndrome before and after 3-month course of PAP-therapy and in 14 subjects without obstructive sleep apnea symptoms. It was found that elimination of hypoxic conditions was associated with an increase in serotonin level. The results demonstrate the effectiveness of PAP-therapy during sleep and allow assessing the role of serotonin as a potential biomarker of intermittent hypoxia during sleep.

[Deletion polymorphism of GSTT1 gene and lipid peroxidation hyperactivation in menopausal insomnia]. / Deletsionnyi polimorfizm GSTT1 i giperaktivatsiya protsessov lipoperoksidatsii pri insomnii klimaktericheskogo perioda.

OBJECTIVE: A comparative analysis of the parameters of lipid peroxidation - antioxidant defense system in menopausal women with- and without insomnia, depending on the GSTT1 polymorphism. MATERIAL AND METHODS: The study included 181 menopausal Caucasian women (ethnic group - Russians), who according to the results of the clinical-anamnestic examinations were divided into insomnia group (n=120, age 53.68±4.61 years, body mass index 26.47±3.73 kg/m2) and control group (n=61, age 52.64±4.91 years, body mass index 27.69±3.11 kg/m2). The insomnia group was formed according to the clinical guidelines for the diagnosis and treatment of chronic insomnia in adults, and scores of the Insomnia Severity Index. The study of the GSTT1 gene polymorphism was carried out using polymerase chain reaction. The lipid peroxidation - antioxidant system parameters were determined by spectrofluorophotometric methods. RESULTS: In the insomnia group, carriers of the normal GSTT1 genotype had higher diene conjugates with lower glutathione peroxidase activity as compared to controls. When comparing groups of women with the deletion in GSTT1, an increase in the content of substrates and lipid peroxidation products was observed at all stages of lipid peroxidation, oxidized glutathione, glutathione S-transferase activity with a decrease in the content of reduced glutathione and retinol in the insomnia group as compared to controls. In the insomnia group, carriers of the deletion genotype had a higher content of ketodienes/conjugated trienes and active products of thiobarbituric acid, a lower content of retinol and α-tocopherol as compared to the patients with normal GSTT1 genotype. Conclusions. Insomnia in the menopausal women is accompanied with the intensification of lipid peroxidation only in the carriers of the GSTT1 deletion genotype.

[Association of polymorphic markers of GSTP1 gene with oxidative stress parameters in infertility men].

Genetic factors cause various forms of male infertility in 30-50% of cases. The role of oxidative stress in male infertility has been broadly recognised, and the search for a new marker to determine the redox environment in semen has gained considerable interest. AIM: to establish the association of two polymorphic loci Ile105Val, Ala114Val of the GSTP1 gene (glutathione transferase class pi-1) with the parameters of oxidative stress in men with infertility. MATERIALS AND METHODS: the main study group consisted of 160 men of reproductive age with infertility (mean age - 29,9+/-5,3 years). The control group included 104 practically healthy men with realized reproductive function (average age - 30,2+/-3,6 years). Molecular and genetic study of polymorphisms of the GSTP1 gene was performed by using real-time PCR. The material for the study was DNA samples, the extraction of which was carried out from samples of whole venous blood. The components of lipid peroxidation and antioxidant protection were determined in the blood and ejaculate using spectrophotofluorometric METHOD: s. Resalts: While analyzing the frequency of occurrence of the Ile105Val polymorphism of the GSTP1 gene in men with infertility and fertile men, statistically significant differences were found at (2=7,487; p=0,024). No significant differences were found between the groups (2=3,823; p=0,14), when were compared the frequency distribution of the genotypes of the Ala114Val polymorphism of the GSTP1 gene in men diagnosed with infertility and fertile patients. In men with infertility, carriers of the GSTP1(Ile105Val) heterozygous polymorphism, associations of the studied gene were established with an increase in GSH activity by 7% and a decrease in GR by 20% in blood and a decrease in SOD activity by 8% in the ejaculate, in contrast, fertile men, carriers of heterozygous polymorphism GSTP1(Ile105Val), which have associations with an increase in total AOA blood by 20% and with a decrease in GPO activity by 24% in the ejaculate. In men with infertility, carriers of the heterozygous polymorphism of GSTP1(Ala114Val), associations of the studied gene were established with a decrease in -tocopherol concentration by 15%, an increase in GPO activity by 25% in blood and a decrease in SOD activity by 7% in ejaculate, in contrast, fertile men, carriers of heterozygous polymorphism GSTP1(l114Val), which have associations with an increase in the concentration of DK in blood by 19% and with a decrease in GST activity by 32% in the ejaculate. CONCLUSION: identification of carriers of polymorphic loci Ile105Val, Ala114Val GSTP1, as well as determination of enzymes of the thiol disulfide system can be recommended for additional assessment of the risk of reproductive disorders in men.

[The association of GSTP1 polymorphisms with male idiopathic infertility].

AIM: To identify the association between Ile105Val, Ala114Val polymorphisms of gene GSTP1 (glutathione transferase pi1) and infertility in Russian men. MATERIALS AND METHODS: A total of 160 infertile Russian men of reproductive age (mean age 30.2+/-3.6 years) were included in study group, while in control group there were 104 age-matched healthy fertile Russian male (mean age 31.3+/-5.4 years). Molecular and genetic studies of Ile105Val, Ala114Val polymorphisms of gene GSTP1 were performed using real-time polymerase chain reaction. Genomic DNA was extracted from the peripheral blood. RESULTS: A frequency of genotypes (p=0.024; df=2; p=0.024) and alleles (z=2,778; p=0,005) of Ile105Val locus was significantly different in the study and control group. In the study group, there was an increase in the frequency of the Ile/Ile genotype by 13% (=3.995; df=1; p=0.046) and a decrease in the frequency of the Val/Val genotype by 6% (=4.887; df=1; p=0.027). A rate of genotype Ile/Ile in infertile men with was 1.7 time higher than in control group (odds ratio (OR):1.73; 95% confidence interval (Cl): 1.04-2.87; p<0.05). There was not significant difference in frequency of genotypes and alleles of Ala114Val polymorphism of gene GSTP1 between the study and control groups. CONCLUSIONS: The male infertility in Russia is associated with Ile105Val polymorphism and not associated with Ala114Val polymorphism of gene GSTP1. In infertile men wild-type genotype and major allele Ile105Val polymorphism of gene GSTP1 were significant more frequent compared to control group. A rate of genotype Ile/Ile in men with infertility was 1.7 time higher.

Predictive Models for the Risk of Dyslipidemia in Adolescents with Essential Arterial Hypertension.

Predictive models of comorbidity, dyslipidemic disorders and essential arterial hypertension, in Russian adolescents aged 12 to 18 years (mean 15.48±1.53) were formulated with consideration for biochemical (lipid profiles) and genetic parameters (carrier state of gene polymorphic variants of apolipoprotein genes ApoA1 (-75G/A and +83C/T), ApoB (Ins/Del), ApoC3 (S1/S2), and ApoE (ε2/ε3/ε4). Significant prognostic risk factors for the mentioned comorbid pathologies were lipid metabolism parameters HDL-Ch, LDL-Ch, VLDL-Ch and carrier state of the +83T allele of the ApoA1 gene and Del allele of the ApoB gene. The obtained mathematical model is characterized by high predictive accuracy: the percentage of correct classification or the rate of correct assignment of each participant to the proper group was 96.33%.

Association of 3111T/C Polymorphism of the Clock Gene with Circadian Rhythm of Melatonin in Menopausal Women with Insomnia.

We carried out a comparative analysis of circadian rhythms of melatonin secretion in Caucasian menopausal women with and without insomnia depending on the 3111T/C polymorphism of the Clock gene. Melatonin levels was measured in the saliva 4 times a day (06.00-07.00, 12.00-13.00, 18.00-19.00, and 23.00-00.00 h). Carriers of the TT genotype with insomnia demonstrated significantly higher level of melatonin in the early morning hours compared to the carriers of the minor allele C (12.60±7.58 and 8.98±8.62 pg/ml, respectively, p=0.023). In the control group, no statistically significant differences were revealed. The carriers of the TT genotype with sleep disorders have higher morning melatonin level compared to control group women (12.60±7.58 and 5.48±4.74 pg/ml, respectively, p=0.005) and low nocturnal melatonin level (6.42±4.97 and 12.52±10.40 pg/ml, respectively, p=0.039).

Role of Glutathione-S-Transferase Family Genes in Male Infertility.

Polymorphisms of xenobiotic detoxification genes GSTT1 and GSTM1 and activity of glutathione system enzymes were studied in men with infertility. The frequency of deletion variant of GSTT1 gene in men with infertility was by 2 times higher than in fertile men. Deletion variant of GSTM1 gene was 1.4-fold more frequent in infertile men than in fertile men. Complete deletion of two genes was found in 19% men with infertility and only in 6% fertile men. The balance of activity of glutathione system enzymes essential for the effective detoxification of exogenous xenobiotics and toxic endogenous metabolites was impaired in infertile carriers of deletion variants of genes. Our results suggest that adaptation mechanisms are disordered in infertile men.

Gene-Gene Interactions of Apolipoprotein Gene Polymorphic Variants in Adolescents with Essential Arterial Hypertension and Dyslipidemia.

Using MDR bioinformatic analysis we studied gene-gene interactions between apolipoprotein genes in adolescents with essential arterial hypertension and dyslipidemia against the background of essential arterial hypertension. Optimal models of gene-gene interactions were formed. The six-locus model was the most significant: (ApoA1(+83T), ApoA1(-75A), ApoB(Del), ApoC3(S2), ApoE(ε2), ApoE(ε4). The maximum synergism in both adolescent groups were shown for allele variants ApoA1(-75A), ApoB(Del), and ApoE(ε4). The maximum contribution to gene-gene interactions entropy was made by allelic polymorphisms ApoA1(-75A) and ApoE(ε4) and (in the comorbid pathology group) for ApoE(ε4)+ApoB(Del).

Features of Lipoperoxidation, Antioxidant Defense, and Thiol/Disulfide System in the Pathogenesis of Infertility in Males, Carriers of Nonfunctional Variants of GSTT1 and GSTM1 Gene Polymorphisms.

Comparative analysis of the parameters of LPO, antioxidant defense (AOD), and the thiol/disulfide system was performed in fertile and infertile males of reproductive age carrying different genotypes of the glutathione system genes. Blood plasma, blood hemolysate, and ejaculate served as specimens for biochemical studies. A decrease in glutathione S-transferase activity was found in blood and ejaculate specimens from fertile and infertile carriers of nonfunctional GSTT1(0/0)/GSTM1(0/0) genotypes. In infertile carriers of nonfunctional GSTT1(0/0)/GSTM1(0/0) genotypes determining reduced glutathione S-transferase activity, a decrease in the concentration of low-molecular-weight cell antioxidant (reduced glutathione) and an increase in the concentration of secondary LPO products (TBA-reactive substances) were revealed. Identification of carriers the polymorphic GSTT1 and GSTM1 variants and analysis of activity of the thiol/disulfide system enzymes can be recommended for additional evaluation of the risk for reproductive dysfunction in men.

[Association of polymorphism of GSTT1 and GSTM1 genes with infertility in men].

AIM: To identify the association between homozygous deletion genotypes of glutathione transferase genes GSTT1 (glutathione transferase theta 1), GSTM1 (glutathione S-transferase mu1) and infertility in Russian men. MATERIALS AND METHODS: The article presents a comparative analysis of the incidence of homozygous deletion genotypes of glutathione transferase genes GSTM1 and GSTT1 in Russian men with and without infertility. The study group comprised 160 infertile Russian men of reproductive age (mean age 30.2+/-3.6 years.) The infertility diagnosis was verified according to the WHO guidelines. The control group comprised 104 healthy Russian volunteers (mean age 31.3+/-5.4 years.) Molecular genetic detection of GSTM1 and GSTT1 deletion polymorphisms was performed using PCR. The genomic DNA for the study was extracted from whole blood samples. RESULTS: The study and control group differed significantly in incidence of GSTM1 (p=0.043) and GSTT1 (p=0.008) deletion polymorphisms. The probability of detecting "zero" genotypes of the GSTT1 and GSTM1 genes in infertile men was 2.5 (p<0.05) and 1.7 times higher (p<0.05), respectively, than in fertile men. CONCLUSIONS: Therefore, the study findings allow us to conclude that the deletion genotypes of GSTM1 and GSTT1 are associated with infertility in Russian men. Molecular genetic analysis of deletion polymorphism of glutathione transferase genes can be recommended for a comprehensive examination of infertile men.

Oxidative Stress and Catalase Gene.

We studied the frequency of alleles and genotypes of CAT gene -262C>T polymorphism (rs1001179) in Russian and Buryat adolescents. The frequency of -262T allele was 28.31% in Russians and 16.84% in Buryats (p<0.01). In both ethnic groups, a correlation between the study polymorphism and concentration of diene conjugates was observed. Carriers of TT-genotype of CAT gene-262C>T polymorphism had lower level of diene conjugates than carriers of CT- and CC-genotypes.

[Polymorphism (353)R>Q of Gene of Blood Clotting Factor FVII and Plasma Hemostasis].

A comparative estimation was conducted to assess the prevalence of genotypes and alleles of the (353)R>Q polymorphism of the coagulation factor FVII gene between a group of the Russian adolescents with essential arterial hypertension and a group of Russian adolescents without such health problems. The RR genotype was diagnosed in 55 adolescents (75.34%) of the control group and in 99 adolescents (84.61%) of the adolescents suffering from essential arterial hypertension (χ2 = 1.949, p = 0.163). The frequency of the R-allel was 85% and 91.9%, respectively (χ2 = 3.110, p = 0.078). The role of the FVII gene in the determination of the F7 plasma activity was defined in adolescents with essential arterial hypertension and holders of different alleles. Holders of the R allele had significantly higher activity of coagulation factor F7 (97.66 ± 15.48 against 83.37 ± 15.16, p = 0.002) and factor F2 (107.45 ± 6.03 against 103.75 ± 6.81, p = 0.023) than holders of the Q allele. This relationship was not found in adolescents of the control group.

Association of Apolipoprotein A1 Gene Polymorphisms with Serum Lipid Spectrum in Adolescents in East Siberia.

We studied the incidence of genotypes of polymorphic alleles (-75)G>A and (+83)C>T of apolipoprotein A1 gene in healthy Russian adolescents, residents of East Siberia. Genotyping was carried out by PCR with subsequent restriction fragment length polymorphism analysis. The incidence of allele (-75)A was 22.5%, of allele (+83)T - 7.3%. Association of allele (-75) A with high blood cholesterol level was revealed.

[Association of (192) Q>R polymorphism of the paraoxonase gene with a lipid profile and components of lipid peroxidation and antioxidant protection in populations of Russians and Buryats from Eastern Siberia].

The distribution of genotypes and alleles of Q192R polymorphism of the paraoxonase1 (rs622) gene was studied in Russian and Buryat populations living in Eastern Siberia. Correlations between genotypes and some parameters of the lipid profile and lipid peroxidation indicators were revealed. In the group of Russians, the frequency of genotypes was QQ-0.354; QR-0.569 and RR-0.077, alleles Q-0.638, and R-0.362. In the group of Buryats, the genotype frequencies were QQ-0.204; QR-0.629 and RR-0.167, alleles Q-0.518, and R-0.482. No differences in allele and genotype frequencies were established between the groups of Russians and Buryats. In the group of Russians, the VLD L cholesterol content (H = 6.461; p = 0.0395) and diene conjugates (H = 8.107; p = 0.0174) was higher in carriers of genotype QQ than in carriers of genotype RR. In the group of Buryats, the HDL cholesterol content (H = 1.548; p = 0.0461) was higher in carriers of genotype QQ, wherein the concentration of malondialdehyde (H = 13.854, p = 0.0010) was lower in comparison with carriers of genotype RR.

[Causes and Factors of Male Infertility].

The preservation of reproductive health of the population is an important factor of demographic policy of the state. According to some authors from 14 to 30% of couples of reproductive age suffer from infertility, malefactor in such marriages is detected in more than half of the cases. As you know, in recent years there has been a significant deterioration in the main indicators of reproductive function of men. Increased the number of andrological diseases, morphological disorders of the male reproductive system, almost halved the production of sperm in men of reproductive age. The reason probably lies behind a whole range ofstressfactors, such as medical ignorance, uncontrolled and inappropriate use of medication, metabolic disturbances, lack of vitamins and minerals, the impact of industrial pollutants, as well as the growth of addictive disorders (alcoholism, smoking and drug addiction). The forms of infertility differ according to its etiology and severity from minor changes to complete spermatogenesis dysfunction of the gonads, and can also occur due to genetic disorders. The lack of analysis of the relationship between clinical and genetic-biochemical components in men with infertility makes it impossible to understand the pathogenesis of infertility and to assess the risks of male infertility. High level of current medicine does not always guarantee an identification of the cause of male infertility. The article analyzes data from the review of specialized literature on the diagnosis and etiopathogenesis of male infertility. Frequency and clinical signs of pathology of the male reproductive system depend on the combinatorial effects of environmental influences, manifested most often in mutually reinforcing effect. A combination of several, seemed to be imperceptible factors makes the risk of development of male reproductive pathology very high. This situation compels specialists to conduct comprehensive studies on the men reproductive potential.

Lipid peroxidation and mitochondrial superoxide dismutase-2 gene in adolescents with essential hypertension.

The study of LPO processes in adolescents of different races with essential hypertension revealed that Mongoloids exhibit oxidative stress by altering the level of the formation of diene conjugates, the primary LPO products. Caucasians increased the levels of both primary and end products of LPO, diene conjugates, and malondialdehyde. The revealed differences can be genetically determined because ethnic differences in the frequency of SOD2 gene Ala16Val polymorphism and its contribution to the biochemical phenotype were reported. The risk factors are Ala allele associated with increased MDA level for adolescent Caucasians and Val allele linked with decreased level of total antioxidant activity for adolescent Mongoloids.

[Genes of antioxidant enzymes].

Oxidative stress plays an important role in the pathogenesis the most of diseases. Important components of protecting cells from oxidative stress are antioxidant enzymes. Antioxidant enzymes are characterized by population differences in enzyme activity. The purpose of the study to summarize and discuss information on genetic polymorphisms of antioxidant enzymes in the most pathology. The development plays of the role of oxidative stress.

[Assesment of Parameters of QT Interval in Children and Adolescents.].

Aim. To determine limits of interval QT in children and adolescents aged 0-17 years and to detect possible ethnic differences of its changes. Material and Method. Twelve lead ECGs were recorded in 1531 subjects without overt cardiovascular pathology (47.2% females, 52.8 males, 57.3% of Slavic and 42.7% of Buryat i.e. mongoloid ethnicity). Results. Corrected QT interval (QTc) exceeded 440, 460 and 480 ms in 2.3, 1.05, and 0.26% of children. Prolongation of QTc was found in 0.46% and 0.11% of Slavic and Buryat children, respectively (p=ns). Starting from the age of 8 years girls had longer QTc than boys (454.1+/-15.2 and 438.3+/-8.4 ms, respectively, p<0.05). QTc less than 350 ms was registered in 12 children (0.78%). Eight of these children with mean QTc 329.1+/-32.3 ms had family history of syncope or sudden death. Variability of absolute QT values was 8+/-14.3 ms (maximally up to 40 ms). Conclusions. QT interval is prolonged when QTc duration exceeds 440 ms in children younger than 8 years and in male adolescents or 460 ms in girls aged 8 years or older and in children during first year of life. QT interval is shortened when QTc is less than 350 ms (1st degree of shortening). In children with QTc below 330 ms (2nd degree of shortening) short QT syndrome should be excluded. Normal variability of absolute QT value during sinus arrhythm on ECG at rest does not exceed 40 ms.

[Impulse low-intensity electromagnetic field in the treatment of adolescents with essential arterial hypertension].

Effectiveness of different regimes of a course exposure to impulse low-intensity electromagnetic field (Infita unit) was studied in 69 adolescents with essential hypertension. A ten-day course of single 9 min procedures with 30 Hz field produced better antihypertensive effects than the regime used in the adults. This treatment provided improvement in bioelectric activity of the brain, mental state, central hemodynamics.