A comparative analysis of melatonin circadian rhythms in Caucasian (incoming population) and Asian (indigenous population) menopausal women with/without sleep disorders depending on the genotype of Clock 3111T/C gene polymorphism was realized.The melatonin level in the saliva was determined four times a day (6:00-7:00, 12:00-13:00, 18:00-19:00, 23:00-00:00 h). The Caucasian women-carriers of the TT-genotype with insomnia as compared to control group-had a higher morning melatonin level and a lower night melatonin level. The Asian women with TT-genotype and insomnia had a lower levels of melatonin as compared to control at daytime, evening and night. A significantly higher melatonin level in the early morning hours was detected in the Caucasian women-carriers of the TT-genotype with insomnia as compared to group womencarriers of the minor 3111C-allele. There were no statistically significant differences in the circadian rhythms of melatonin in the Asian women depending on the genotype of the Clock 3111T/C polymorphism. An assumption with respect to the protective role of the minor allele 3111C in the development of insomnia associated with the displacement of melatonin circadian rhythms in the representatives of the incoming population was made.

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.

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.

В настоящее время проблемы здоровья населения стра-ны, рождаемости и перспективы демографии -ключевые не только в России, но и за рубежом. Неблагоприятные демографические показатели с устойчивым отрицательным коэффициентом естественного прироста населения в по-следние десятилетия заставляют специалистов различного профиля (генетиков, морфологов, иммунологов, эндокри-нологов, гинекологов, урологов) обратиться к анализу фак-торов, влияющих на рождаемость, среди которых важное место занимает бесплодие [1][2][3]. Согласно статистическим данным, частота бесплодных браков во многих странах мира колеблется от 8 до 29%. В Европе бесплодием страдает око-ло 10% супружеских пар, в США -15%, в Канаде -17%, доля бесплодных браков в России варьирует от 8,2 до 19,6%. Приведенные показатели превышают критический уровень (15%) и представляют государственную проблему, имея много составляющих (социально-демографическую, ме-дицинскую, экономическую и др.) [1][2][3]

The aim of this research was to investigate the glutathione system components and their association with polymorphisms GST genes in men with infertility.Materials and Methods: One hundred and sixty Russian men of reproductive age (Caucasians) who came to the public health institution Republican Perinatal Center in Ulan-Ude with an infertility problem of one year and more after marriage were included in the main group. The control group included 104 men with proven fertility. DNA samples were genotyped for polymorphisms in GSTP1, GSTT1 and GSTM1genes and activity of glutathione system enzymes was determined.Results: The most informative genetic and metabolic indicators in Caucasian males with infertility were combinations of the null genotypes GSTT1(*0/*0)+GSTM1(*0/*0) associated with a decrease of GST activity in blood and ejaculate and an increase of GSH and GPO in the blood. Another combination is GSTP1(Ile105Val)+GSTP1(Ala114Val), which is associated with suppression of the blood and ejaculate GPO activity and a decrease in blood concentration of GSH.

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.

Comparative analysis of the frequency distributions of genotypes and alleles of 3111T/C Clock gene polymorphism was carried out in climacteric Caucasian women with and without insomnia. Genotype TT is more incident in women with insomnia (55.5% vs. 42.6% in the control). Allele T predominated in the control and study group and its frequency is higher in women with insomnia. The OR for the risk of insomnia realization is 1.78 (95%CI 1.16-2.75). No association between genotypes and complaints of patients with insomnia is detected.

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.