The problem of iodine deficiency in the ecosystems of Yakutia has a serious impact on human and animal health, affects vital processes and causes damage to agriculture, which requires systematic study. The aim of this study is to investigate the processes of iodine cycling in various components of the ecosystem, including air, soil, water, plants and animals. Research in this direction is becoming increasingly important in view of the widespread problem of iodine deficiency, which affects both the health of the local population and production activities in agriculture. In order to gain an in-deep understanding of the iodine cycle in the ecosystems of Yakutia, the study was conducted in various biogeochemical provinces identified on the basis of landscape and soil criteria. Laboratory methods of biochemical analysis included the kinetic rhodanide-nitrite method, the titrimetric method and the oxidation reaction of the rhodanide ion. The study of the iodine content in the studied components of the ecosystems of Yakutia revealed significant differences in its concentration in various types of water and soils, depending on the biogeochemical characteristics of the provinces. Pasture plants in the Central Yakutia province had a significantly low iodine content than in the Kolyma province, which does not meet the needs of local livestock. This is a potential problem for livestock production and is related to the general trends in iodine concentration in the soils of this province. In general, these results highlight the importance of understanding the biogeochemical characteristics of ecosystems in order to develop effective strategies for managing iodine content in order to ensure human and animal health in Yakutia.

The aim of this study is to conduct a comparative analysis of average irisin levels between female and male (with normal weight and obese) to assess sexual dimorphism. Circulating levels of irisin in the blood of 279 Yakuts (185 female, 94 male, average age 19.8 +/- 2.03 years) were determined. A comparative analysis of irisin levels between male and female in three BMI groups (underweight, normal weight, overweight/obesity) was carried out. The average level of irisin in the blood plasma in female was 8.33 +/- 2.74 mcg/mL, and in male 7.76 +/- 1.86 mcg/mL. Sexual dimorphism (p = 0.02) was detected in Yakuts with normal weight, where the level of irisin was higher in women (8.42 = 2.92 mcg/mL) compared to men (7.51 = 1.61 mcg/mL). Conducted a comparative analysis of irisin levels between male and female based on global data, were including this analysis are 2132 people. The age of the participants ranged from 18 to 61 years old. The meta-analysis was carried out for two different BMI groups: the first group included people with normal weight (18.5-24.9 kg/m(2)), the second group included people with varying degrees of obesity (>30 kg/m(2)). Comparative analysis of irisin levels in a large sample revealed statistically significant sexual dimorphism, where irisin levels were also higher in female compared to male, only in a sample of obese people (p = 0.02), in a sample of people with normal weight, no sexual differences were found (p = 0.09). Thus, the influence of obesity on sexual dimorphism was revealed.

The aim of this study was to assess the levels of testosterone in serum as a function of body mass index (BMI, 15-30 kg/m2) in young men in Yakutia, aged 18 to 28. The total sample (n=87) was subdivided into three BMI groups: underweight (n=11), normal weight (n=64), and overweight (n=12). It was found that underweight in young men does not affect the level of testosterone in the blood. Thus, no significant differences in testosterone levels were found between the groups of men with underweight (23.06 +/- 5.66 nmol/L) and those with normal weight (22.9 +/- 8.24 nmol/L; p=0.703). In contrast, being overweight and obese led to lower testosterone levels. Thus, in overweight individuals, testosterone levels were significantly lower (18.54 +/- 5.73 nmol/L), compared with those who had an underweight (23.06 +/- 5.66 nmol/L; p=0.04) or the weight was normal (22.9 +/- 8.24 nmol/L; p=0.03). A comparative analysis of testosterone levels based on global data was conducted, including 1866 men. The age of the participants ranged from 18 to 30 years old. The control group comprised 528 men with normal body weight (18.5-24.99 kg/m2), and a group with an excess of overweight and obese (25-35 kg/m2) 1338 men were included. The results of testosterone level according to global data confirmed the inverse correlation of a decrease in testosterone levels with an increase in BMI (p<0.01). The assessment of heterogeneity of studies in the "Overweight/obese" subgroup was I2=46% (average heterogeneity), and in the "Normal weight" subgroup heterogeneity was I2=3% (unimportant heterogeneity), such insignificant heterogeneity in both subgroups may indicate a negative correlation of testosterone levels with BMI, regardless of race and ethnicity.

The article presents the results of the diagnostic search of the hereditary autosomal recessive disease Pendred's syndrome (sensorineural deafness combined with thyroid disorders) in patients with hearing disorders in Buryatia using instrumental (threshold tone audiometry) and laboratory methods (ELISA analysis of FT3, FT4 and TSH). Threshold tonal audiometry and analysis of thyroid hormone levels were performed in 164 patients with hearing impairment. The analysis showed that 7.9% (13 out of 164 people) of patients with severe hearing loss and deafness can be assumed to have thyroid disorders (12 people - hypothyroidism, 1 person - hyperthyroidism). Overall, 7.3% of deaf patients with hypothyroidism (12 of 164) were formally consistent with the clinical features characteristic of Pendred's syndrome.

Опухолевые маркеры являются интегральными биохимическими показателями общего состояния здоровья организма. Они количественно отражают любые повреждения тканей и органов, требующие восстановления клеточного гомеостаза. Нами было обследовано 250 жителей Республики Саха (Якутия) из которых 80 мужчины, 170 женщин. В сыворотке крови были определены следующие онкологические маркеры: альфа-фетопротеин (АФП), простат-специфический антиген (ПСА), онкомаркер яичников (СА125). Результаты нашего исследования показали, что уровень АФП в сыворотке крови повышен у одиноких, имеющих низкий уровень образованности, работающих, страдающих ожирением. Значение онкомаркера СА125 в организме женщин повышается в зависимости от длительности супружеского стажа, неблагоустроенности жилья, низкого уровня материального благополучия. Концентрация ПСА достоверно увеличена в организме курящих мужчин. Tumor markers are integral biochemical indicators of the general health of the body. They quantitatively reflect any damage to tissues and organs that require the restoration of cellular homeostasis. We examined 250 residents of the Republic of Sakha (Yakutia), of which 80 were men, 170 were women. The following oncological markers were determined in blood serum: alpha-fetoprotein (AFP), prostate-specific antigen (PSA), ovarian tumor marker (CA125). The results of our study showed that the serum AFP level is increased in lonely, with a low level of education, working, obese. The value of the CA125 tumor marker in the body of women increases depending on the duration of marital experience, poor housing conditions, and a low level of material well-being. The PSA concentration is significantly increased in the body of male smokers.

На основе материалов тотальной переписи населения (2010 г.) проведен анализ распространенности языка жестов в России. Полученные результаты сопоставлены с имеющимися данными о частоте наследуемых форм потери слуха на территории России. The paper presents the results of an analysis of the prevalence of sign language (SL) in Russia collected during the 2010 total census, as well as their comparison with data on the frequency of hereditary forms of hearing loss.

The aim of this study is to evaluate the leptin level circulating in blood serum depending on the body mass index (BMI) in young healthy Yakuts (mean age 19.8 +/- 1.5 years). The total sample (n=281) was divided into three groups according to the WHO classification: persons with underweight, normal, overweight / obese. There were no statistically significant differences in BMI between men and women in the groups. As a result of the comparative analysis, it was found that both in women and in men, leptin levels were statistically higher in overweight/obese individuals compared with the other two groups. There were no statistically significant differences in leptin levels between the groups of people with underweight and normal weight, both in women and in men, which could be associated with the body's protection from low temperatures through the development of active brown adipose tissue, secreting additional leptin.

We present the results of analysis of skin epidermis thickness in individuals with recessive mutation c.-23+1G>A in the GJB2 gene in comparison with individuals without this mutation living in Eastern Siberia (Yakut population). We examined 152 individuals with different genotypes by GJB2 gene mutation c.-23+1G>A . Homozygotes and heterozygotes by c.-23+1G>A have thicker epidermal layer (0.245 mm and 0.269 mm, respectively) in comparison with individuals without this mutation (0.193 mm) ( p <0.05). The obtained data support the hypothesis about selective advantage of carriers of mutant GJB2 gene alleles and partly explain extremely high carrier frequency (10.3%) of c.-23+1G>A mutation in the GJB2 gene in Yakut population in Eastern Siberia.

A total of 675 residents aged 18 to 79 years living in 6 different regions of the Republic of Sakha (Yakutia), 461 men and 214 women were examined. The purpose of the study was to assess the extent of the relationship between the level of tumor markers, depending on the rigidity of used water. The concentration of tumor markers in blood serum was determined by the method of enzyme immunoassay. 54.1% of all surveyed people use unpurified water for drinking purposes. Of the six surveyed areas in only three (Namsky District, Verkhnekolymsky District, Aldansky District), the water hardness level corresponded to the norm. The correlation analysis found significant direct correlation between the level of tumor markers and water hardness: AFP (r = 0.134, p = 0.000), CEA (r = 0.211, p = 0.000), PSA (r = 0.360, p = 0.000) and CA-125 (r = 0.290, p = 0.000).

На гормональный фон влияют стресс, личность и курение, тем не менее немногие исследования контролировали или оценивали, как показатели этих факторов взаимодействуют друг с другом. Цель настоящего исследования заключалась в анализе уровней кортизола и дегидроэпиандростерона в зависимости отстатуса курения и базальных черт личности у якутов. Задачами исследования являлись анализ уровня ДГЭА и кортизола в зависимости от курения, анализ психологических параметров у курящих и некурящих лиц и корреляционный анализ линейной зависимости уровней кортизола и ДГЭА в зависимости от нейротизма иэкстраверсии у курящих и некурящих мужчин. В исследовании приняло участие 116 здоровых мужчин-якутов, средний возраст которых составил 21,5±2,25 год. Выборка была разделена на две группы: курящие (n=36) и не курящие (n=80). Определение уровней кортизола и ДГЭА в сыворотке крови проводилосьиммуноферментным методом. Статус курения определялся по оригинальной анкете с информацией об основных социально-демографических характеристиках. Для диагностики экстраверсии и нейротизма был использован личностный опросник Айзенка. Статистический анализ проведен с использованием программного пакетаSTATISTICA, версия 8.0. Выявлено статистически значимое повышение уровня кортизола у курящих (11,52 мкг/дл) по сравнению с некурящими (9,28 мкг/дл) (р=0,02). Установлено, что средний ранг экстраверсии и нейротизма выше у курильщиков, чем у некурильщиков (экстраверсия: 12,91 и 11,50 соответственно, р=0,04; нейротизм: 13,13 и 11,36 соответственно, р=0,04). Обнаружено преобладание холерического (39%) и сангвинического (33%) типа темперамента в группе курящих по сравнению с некурящими (22% и 20%, соответственно). Подверженность курению у экстравертов можно объяснить основными личностными чертами, характерными для этого типа темперамента (импульсивность, общительность, тяга к новым впечатлениям). Показана зависимость содержания ДГЭА в сыворотке крови у курящих мужчин от показателей экстраверсии (r=0,47; р=0,02): чем более выражено значение экстраверсии, тем выше уровень ДГЭА. Таким образом, проведенное исследование показывает, что у мужчин-якутов статус курения влияет на уровень стероидных гормонов (повышает уровень кортизола и снижает уровень ДГЭА) и связан с психологическими параметрами (экстраверсией и нейротизмом).

Autosomal recessive deafness type 1A (DFNB1A) caused by mutations in the GJB2 gene (Cx26) is the main cause of nonsyndromic hearing impairment in many populations worldwide. It is considered that widespread prevalence of DFNB1A can be due to the long tradition of intermarriages between deaf people (assortative marriages) combined with their increased social adaptation and genetic fitness after widespread introduction of sign language. For the first time, the data on mating structure and reproduction of deaf people living in Yakutia (Eastern Siberia, Russia) are presented in comparison with contribution of the GJB2 gene mutations to the etiology of hearing impairment. The relative fertility of deaf people compared to their hearing siblings is 0.78 (mean number of children 1.76 ± 0.10 and 2.24 ± 0.09 to deaf and their hearing siblings, respectively, p = 0.0018). The rate of assortative marriages among deaf people is 77.1% (81 of 105 marriages). Biallelic mutations in the GJB2 gene were found in 42.2% (43 of 102) of examined deaf people, which corresponded to diagnosis DFNB1A for these patients. A comparison of deaf marital partners by GJB2 status revealed a proportion of noncomplementary marriages (24%) in which hearing loss in both partners was caused by the presence of biallelic GJB2 gene mutations resulting in the birth of only deaf children in such couples. Thus, the set of obtained data including a relatively high genetic fitness (expressed as relative fertility) of deaf people in Yakutia in combination with a high rate of assortative marriages among them and high incidence of DFNB1A indicates a possible weakening of selection against such trait as “deafness” and a possible increase in the frequency of GJB2 mutant alleles in subsequent generations.

The high carrier frequency of c.-23+1G>A mutation in the GJB2 gene in Yakut population is might be explained not only by the factors of population dynamics (founder effect, genetic drift, small effective population size), but also can be due to the selective advantage of heterozygous mutations in the GJB2 gene. Because the GJB2 gene is expressed not only in the cochlea but also in other tissues, and in vitro studies conducted on cell cultures show that GJB2-mutant cells were more resistant to the infection of dysentery - Shigella flexneri. The aim of this study is the analysis of the resistance in heterozygous carriers of the c.-23+1G>A mutation in GJB2 gene to diarrhea. Material and methods. We examined 272 Yakut individuals, which was divided into two groups: the first group consisted from 238 individuals without c.-23+1G>A mutation, the second group consisted from 34 individuals with c.-23+1G>A mutation in heterozygous state. All respondents independently filled information about the number of cases of diarrhea in the last year, and indicated the most characteristic form of their stool. Results and Discussion. In heterozygous carriers of the c.-23+1G>A mutation the cases of diarrhea in the last year were not registered in 22% of individuals, in individuals without mutation cases of diarrhea were not registered in 5% of individuals. According to the results of this study heterozygous carriers of the c.-23+1G>A mutation statistically significantly are less susceptible to diarrhea cases than individuals without this mutation. Thus, the obtained results can support the hypothesis about selective advantage of the GJB2 gene mutant alleles carriers and partly explain the extremely high carrier frequency (10.3%) of the c.-23+1G>A mutation in the GJB2 gene in Yakut population.

The c.-23+1G>A splice site mutation is one of the most frequent mutations of gene GJB2 (Cx26, 13q11-q12) associated with congenital non-syndromic autosomal recessive deafness. This mutation is characterized by a wide spread from Eastern Siberia and Central Asia to Eastern Europe, the Middle East, and South Asia. It is currently unknown whether this mutation spread over such a vast territory as a result of the founder effect or there were several local centers of origin of this mutation. For the first time, on the basis of the analysis of variability of nine SNP markers, five different haplotypes in deaf patients homozygous for mutation c.-23+1G>A from six Eurasian populations were reconstructed. The structure of the haplotypes revealed in Yakuts, Russians, Evenks, Tuvinians, Mongols, and Turks makes it possible to assume that mutation c.-23+1G>A (GJB2) could have spread across Eurasia as a result of the founder effect. The greatest diversity of haplotypes with c.-23+1G>A was found in patients from Mongolia, which probably refers to the earlier period of expansion of haplotypes carrying this mutation on the territory of Central Asia.

Тhe DNA testing of autosomal recessive deafness type 1A (DFNB1A, MIM 220290) is complicated when deaf patients have only monoallelic (heterozygous) recessive mutations in the GJB2 (Сх26) gene that is uninformative for establishment of diagnosis. Such patients may be “random” heterozygous carriers of GJB2 mutations as well as have the mutant allele in a cis-regulatory region of GJB2 gene, in element genes encoding other connexins: GJB6 (Сх30) or GJB3 (Сх31). Previous studies of genetic causes of hearing loss in patients from Yakutia were directed to search for only mutations in the GJB2 gene, and the DNA diagnostics was uninformative for 9.7% (38/393) of the patients with monoallelic GJB2 mutations. In this work the search for mutations in genes GJB3 and GJB6 and two deletions с.del(GJB6-D13S1830) and с.del(GJB6-D13S1854) to the cis-regulatory region of GJB2 gene was conducted in 35 patients with GJB2 monoallelic mutations and in 104 normal hearing individuals. The genes studied are two synonymous substitution c.489G>A (р.Leu163Leu) (GJB6) and c.357C>T (р.Asn119Asn) (GJB3) have been found, probably do not have clinical significance, and two nonsynonymous substitution c.301G>A (p.Glu101Lys) (GJB6) and с.580G>A (p.Ala194Thr) (GJB3). Additional experimental evidences are needed for confirmation of pathogenic significance of detected nonsynonymous substitutions in development of hearing loss in studied patients. Diagnosis of the DFNB1A was confirmed in only one patient, who was discovered by the deletion с.del(GJB6-D13S1830) (GJB2) in combination with a recessive mutation с.35delG (GJB2). In general, our results indicate low contribution of mutations in genes GJB6 and GJB3 in hearing loss etiology in Yakutia.

It has been established that the mutation m.1555A>G in the MT-RNR1 gene in the homoplasmic state is associated with non-syndromic sensorineural hearing loss caused by the use of aminoglycoside antibiotics in many families of different ethnic origin. Earlier, the m.1555A>G mutation was detected on a small sample of patients (n = 65) in Yakutia with a frequency of 1.54%. In this study, we performed a search of the m.1555A>G mutation among additional sample of 108 hearing impaired individuals from Yakutia (Eastern Siberia, Russia) As a result, we found no mutation in this sample. When combining both samples (n=65 and n=108), the m.1555A>G mutation frequency in Yakutia is - 0.57% (1/173), and among the Yakut patients frequency of this mutation is 0.92% (1/108). The frequency of the m.1555A>G mutation among deaf patients in Yakutia is 0.57%, and is relatively low when compared with the global data.

Currently, in the HGMD database (The Human Gene Mutation Database) in the GJB2 gene, coding protein connexin 26 (Cx26), 390 different nucleotide changes have been announced, most of which are associated with deafness, of which 73% are single nucleotide (missense/nonsense) variants. The pathogenetic role of most nonsense substitutions is obvious, as they lead to premature termination of translation and interruption of protein synthesis. It is more difficult to assess the mechanism of action of the missens replacement on protein, since they may have a damaging/partially damaging or neutral effect, depending on the location in the amino acid sequence of the polypeptide chain. To assess the possible effect of amino acid substitutions on the structure and/or function of the protein, in the absence of structural and functional studies, the in silica prognostic method is used, which is completely performed by simulation computer programs. In this study, based on the established clinical significance, 7 missense variants of the GJB2 gene, detected as a result of the molecular genetics study of congenital deafness in Yakutia, 9 computer-in silica predictive programs were tested. In order to identify the program with the most accurate prediction of the clinical significance of missense variants substitutions of the GJB2 gene, a comparative analysis of the informative parameters (accuracy, sensitivity and specificity) was carried out with the calculation of the correlation coefficient between the known clinical values of missense variants with in silica evaluation by the programs. In total, of the 9 analyzed programs, the most accurate in silica predictive estimates of the clinical significance of missense variants of the GJB2 gene were given by two programs - SIFT and PROVEAN (R = 0,73). The results obtained can help in carrying out bioinformatic analysis, in the case of detection of missense variants substitutions of the GJB2 gene, which were not described before in the literature.