Six isoforms of uncoupling proteins (UCPs) exist, spanning from UCP1 to UCP6. A precise physiological function has only been established for UCP1, which is involved in non-shivering thermogenesis, but the functions of other UCPs are still not fully defined. Therefore, the purpose of the present study is to search for indications of the involvement of nine polymorphic variants of UCP1-6 genes in human adaptation to cold climates using four criteria: (1) the presence of associations of polymorphic variants of UCP genes with levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine; (2) the presence of associations of polymorphic variants of UCP genes with changes in thyroid homeostasis (SPINA); (3) the presence of associations of polymorphic variants of UCP genes with body surface area; (4) the presence of signals of directional selection to cold climate for polymorphic variants of UCP genes. As a result of the evaluation, the highest scores for cold adaptation traits were recorded for polymorphic variants rs3811787 of the UCP1 gene and rs1800849 of the UCP3 gene. We suggest that the results obtained indicate the importance of uncoupling proteins UCP1 and UCP3 in human adaptation to cold through processes of non-shivering and shivering thermogenesis.

Previously only two families were known with progressive autosomal recessive deafness 103 (DFNB103, OMIM616042) caused by pathogenic variants of the CLIC5 gene. In this study we present the novel truncating variant c.644 G > A p.(Trp215*) of this gene which was found in homozygous state among 22 patients with hearing loss (HL) from 16 unrelated families living in the Sakha Republic of Russia (Eastern Siberia). Genotype-phenotype analysis in patients with DFNB103 showed that HL was sensorineural, symmetrical and variable by severity (from moderate to profound). Audiograms mostly have a down curve configuration, with pronounced loss of high and mid frequencies. In most cases this form of HL was detected in the post-lingual period (mean age 7.9 ± 1.2 years) and has a significant severity progression with age. In average the patients with DFNB103 lost 7.4 ± 13.65 dB on the speech frequency range in pure tone averages (PTA0.5,1.0,2.0,4.0 kHz) per year until reaching profound deafness in the second or third decade of the life. The high frequency of c.644 G > A p.(Trp215*) was found among Siberian GJB2-negative patients (9.9

The aim of this study is to analyze the polymorphism rs689466 of the PTGS2 gene with the level of irisin in blood plasma in the population of Yakuts living in cold climatic conditions. Irisin levels in men with TT genotype (8.2 ± 1.85 μg/ml) were significantly higher compared to men with CT+CC genotypes (7.1 ± 1.25 μg/ml; U=261; p = 0.005). In addition, men with the TT genotype had lower weight (63.6 ± 6.67 kg) than men with the CT+CC genotypes (67.93 ± 7.28 kg; U=279; p = 0.01). The detected association of the TT rs689466 genotype of the PTGS2 gene with elevated irisin levels and with a lower weight in men may indicate the effect of prostaglandin E2 on shivering thermogenesis during cold stress, which may play a role in human adaptation to cold climate.

In the previous study, we found a high prevalence of the m.1555A>G variant of the MT-RNR1 gene, which causes mitochondrial hearing loss (OMIM 561000) among deaf patients living in the Baikal Lake region. In this regard, in the present study, a genotype-phenotypic analysis of the hearing function in individuals with the m.1555A>G variant was carried out in the discovered Siberian region. Clinical and audiological analysis was performed in 48 people with this mitochondrial variant, whose average age was 51.3±15.5 years. The obtained genotype-phenotypic data are consistent with previously conducted studies of the features of the auditory function in individuals with m.1555A>G, which note incomplete penetrance of the manifestation of the pathological phenotype. Of particular interest in our cohort are three cases of mixed hearing loss, including both sensorineural (inner ear defect) and conductive (middle ear defect) components. We do not exclude the possibility that the detected clinical signs may be a consequence of systemic damage to the hearing organ in this mitochondrial variant. On the other hand, the detected cases may be associated with a cross-pathological effect caused by another form of a less common or rare disease, which requires further molecular genetic studies.

Mitochondrial forms account approximately 1–2% of all nonsyndromic cases of hearing loss (HL). One of the most common causative variants of mtDNA is the m.1555A > G variant of the MT-RNR1 gene (OMIM 561000). Currently the detection of the m.1555A > G variant of the MT-RNR1 gene is not included in all research protocols. In this study this variant was screened among 165 patients with HL from the Republic of Buryatia, located in the Baikal Lake region of Russia. In our study, the total contribution of the m.1555A > G variant to the etiology of HL was 12.7% (21/165), while the update global prevalence of this variant is 1.8% (863/47,328). The m.1555A > G variant was notably more prevalent in Buryat (20.2%) than in Russian patients (1.3%). Mitogenome analysis in 14 unrelated Buryat families carrying the m.1555A > G variant revealed a predominant lineage: in 13 families, a cluster affiliated with sub-haplogroup A5b (92.9%) was identified, while one family had the D5a2a1 lineage (7.1%). In a Russian family with the m.1555A > G variant the lineage affiliated with sub-haplogroup F1a1d was found. Considering that more than 90% of Buryat families with the m.1555A > G variant belong to the single maternal lineage cluster we conclude that high prevalence of this variant in patients with HL in the Baikal Lake region can be attributed to a founder effect.

In this study, analysis of the mitochondrial gene pool structure of residents of the village of Russkoye Ust’ye was carried out. It was revealed that the spectrum of mitochondrial lines of the Russian old-settlers is represented by eight haplogroups and is characterized by the dominance of East Eurasian lineages C, D, G, F, and M13, which amounted to 66.7

The aim of the study was to search for seasonal variations in the levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) in young men in Yakutia, where there are strong changes in climatic parameters in the winter-spring period (from -41.8°C to -0.2°C). Seasonal variations between winter and spring were found for fT3, where in winter its levels were lower – 6.48±0.31 pmol/L than in spring – 6.88±0.1 pmol/L (p=0.005). There were no statistically significant seasonal variations for TSH (U=97; p=0.914) and sv.T4 (U=47; p=0.112). Winter-spring seasonal variations of fT3 detected in this study there are signs of polar T3 syndrome in young men in Yakutia. To search for the causes of the detected seasonal variation, a correlation analysis of the levels of TSH, fT3 and fT4 was carried out depending on daylength and atmospheric air temperature. As a result, a correlation between fT3 and fT4 with the daylight (fT3: R=0.339, p=0.03; fT4: R=-0.346, p=0.01) and with air temperature (fT3: R=0.295, p=0.05; fT4: R=-0.296, p=0.04). No correlations were found with TSH levels (daylight: R=-0.06, p=0.69; air temperature: R=-0.09, p=0.559). Thus, the residents of Yakutia have signs of polar T3 syndrome, which can be associated with both a short light day and low atmospheric temperatures in winter. The results obtained may indicate an increase in the absorption of T3 at the tissue level when exposed to cold. Keywords: thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), Yakutia, polar T3 syndrome.

Type 2 thyroid allostasis is a dynamic stress response to changes in thyroid homeostasis that may occur in response to chronic exposure to cold. It is believed that, under these conditions, type 2 allostatic reactions can increase the basal metabolic rate to maintain priority thermogenic mechanisms in the body. For the first time, this work assesses the allostatic response of the thyroid gland among residents of the central region Yakutia with the most extreme climate (from -47°С to -11°С) using a mathematical model called SPINA. The SPINA model reflects the total activity of peripheral deiodinase enzymes (SPINA-GD), as well as the secretory capacity of the thyroid (SPINA-GT). The results showed that the SPINA-GT parameter was within normal limits for all individuals in the study. However, the SPINA-GD parameter was also within normal limits in 30% of those examined, with an increased SPINA-GD value found in 70% of the individuals examined. It was revealed that individuals with elevated SPINA-GD had higher free triiodothyronine (fT3) levels (6.79±0.62 pmol/L) and lower free thyroxine (fT4) levels (13.82±1.51 pmol/L) than those with normal SPINA-GD (fT3=5.96±0.48 pmol/L; fT4=15.37±0.98 pmol/L; p<0.001). This indicates an increased rate of T4 deiodination to T3 in 70% of the most individuals, and the reason for this is likely due to type 2 thyroid allostasis in response to cold stress. Using the SPINA parameters for the first time allows us to identify changes in hypothalamus-pituitary-thyroid axis homeostasis during the winter-spring season among 70% of surveyed residents of Eastern Siberia. Keywords: type 2 thyroid allostasis, SPINA-GT, SPINA-GD, free triiodothyronine (fT3), free thyroxine (fT4), Yakutia.

The arginine vasopressin receptor gene (AVPR1A) is one of the genes affecting mental processes. The aim of this study was to search for associations of microsatellite locus RS1, which is related to the AVPR1A expression level, with the level of hormones of the anterior pituitary gland and personality traits. The study sample included Yakut men aged 18–26 years (n = 121). The analysis of RS1 locus was carried out using the PCR method and sequencing of the primary nucleotide sequence. Serum hormonal levels of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin were determined by the time-resolved fluorescence immunoassay (DELFIA), plasma adrenocorticotropic hormone (ACTH) levels were determined by enzyme-linked immunosorbent assay (ELISA). In the Yakut population “short” (S) alleles of the AVPR1A RS1 locus containing ≤ 10 repeats (63

The audiological features of hearing loss (HL) in patients with autosomal recessive deafness type 1A (DFNB1A) caused by splice site variants of the GJB2 gene are less studied than those of patients with other variants of this gene. In this study, we present the audiological features of DFNB1A in a large cohort of 134 patients with the homozygous splice site variant c.-23+1G>A and 34 patients with other biallelic GJB2 genotypes (n = 168 patients with DFNB1A). We found that the preservation of hearing thresholds in the speech frequency range (PTA0.5,1.0,2.0,4.0 kHz) in patients with the c.[-23+1G>A];[-23+1G>A] genotype is significantly better than in patients with the “severe” c.[35delG];[35delG] genotype (p = 0.005) and significantly worse than in patients with the “mild” c.[109G>A];[109G>A] genotype (p = 0.041). This finding indicates a “medium” pathological effect of this splice site variant on hearing function. A detailed clinical and audiological analysis showed that in patients with the c.[-23+1G>A];[-23+1G>A] genotype, HL is characterized as congenital or early onset (57.5% onset before 12 months), sensorineural (97.8%), bilateral, symmetrical (82.8%), variable in severity (from mild to profound HL, median hearing threshold in PTA0.5,1.0,2.0,4.0 kHz is 86.73±21.98 dB), with an extremely “flat” audioprofile, and with a tendency toward slow progression (a positive correlation of hearing thresholds with age, r = 0.144, p = 0.041). In addition, we found that the hearing thresholds in PTA0.5,1.0,2.0,4.0 kHz were significantly better preserved in females (82.34 dB) than in males (90.62 dB) (p = 0.001). We can conclude that in patients with DFNB1A caused by the c.-23+1G>A variant, male sex is associated with deteriorating auditory function; in contrast, female sex is a protective factor.

In the world the role of pathogenic variants of the MYO15A gene in the etiology of hearing loss has not been sufficiently studied, since the large size of the gene (66 exons, 71 kb) suggests the search for pathogenic variants using NGS technologies, which are not yet sufficiently used in routine practice. In this regard, it is relevant to study the role of pathogenic variants of the MYO15A gene in the etiology of non-syndromic forms of hearing impairments. The purpose of this work is to describe the rare pathogenic variant c.7636C>T p.(Gln2546*) in the MYO15A gene, found in a homozygous state in two siblings with prelingual profound sensorineural hearing loss from a Buryat family. Previously, this variant was found only in one patient in a compound-heterozygous state with another nonsense variant in the MYO15A gene in Brazil and described as pathogenic. Detection of variant c.7636C>T p.(Gln2546*) in a homozygous state in Buryat siblings may indicate either a rare case of endogamous marriage or a wider distribution of this variant in the Lake Baikal region. Keywords: autosomal recessive deafness (DFNB3), MYO15A gene, variant c.7636C>T p.(Gln2546*), Republic of Buryatia.

The purpose of this study is to test the hypothesis that personality traits and stressful situations experienced in childhood could be associated with the level of serum cortisol. The sample included 121 healthy adult men of Yakut (Sakha) ethnicity aged 18 to 27 years. To assess personality traits, the TCI temperament and character questionnaire by R. Cloninger was used. Serum cortisol levels were assessed by enzyme-linked immunosorbent assay (ELISA). It was found that such a temperament trait as “reward dependence” is associated with higher level of cortisol in the blood (p = 0.04). Experienced stressful situations are associated with the character trait “self-transcendence” (p = 0.049) but do not significantly affect cortisol levels. In individuals with high levels of stress, significant correlations were found between the “novelty seeking” (r = 0.33) and “self-directedness” (r = 0.36) with serum cortisol levels, which may reflect the prolonged effect of stress on increasing the sensitivity of the adrenal cortex. The results indicate a possible connection between one of the human temperament traits “reward dependence” and higher levels of cortisol in the blood. A high level of experienced stress situations reduces scores on the character trait “self-transcendence.”

In this work, we searched for the missense variant c.757A>G p.(Ile253Val) of the SLC26A4 gene in GJB2-negative patients with hearing loss (n=201) and in the control group of hearing individuals (n=103) in Yakutia. As a result, this variant was detected with a frequency of 2.02% among patients, in the control group 1.94%. To interpretation the clinical significance, a frequency analysis of this variant and in silico evaluation were performed, the results of which are in favor of the likely benign of the c.757A>G p.(Ile253Val) variant of the SLC26A4 gene, as indicated by the high frequency of occurrence in population samples, and the fact that this missense substitution theoretically does not violate the structural stability of the pendrin protein (SLC26A4).

Pathogenic variants of mitochondrial tRNA genes remain poorly understood in the context of the study of the etiology of hearing loss, despite the fact that they are one of the important causes of syndromic and non-syndromic hearing impairment as well as aminoglycoside-induced hearing loss. In this work, we searched for pathogenic variants of the mtDNA MT-TS1 gene in patients with hearing impairments in Buryatia. One rare variant m.7445A>C was found in the MT-TS1 gene out of five investigated variants in one patient (1/165; 0.6%). This variant is localized in the coding region of two genes the MT-CO1 (H-chain) and MT-TS1 (L-chain), but on different mtDNA chains. However, a pathogenetic role for the m.7445A>C substitution has been shown for the MT-TS1 gene, but not for the MT-CO1 gene. In databases, the m.7445A>C variant is associated with nonsyndromic hearing loss, including those caused by aminoglycoside antibiotics. A comparative genotype-phenotypic analysis of our case and four cases with m.7445A>C of the MT-TS1 gene described earlier in the literature showed that hearing loss in all cases is not congenital, but at the same time varies in severity with low penetrance. The results obtained indicate the involvement of other modulating factors in the clinical manifestation of hearing impairment associated with this variant. Thus, further study of rare variants of MT-TS1 gene will contribute to our understanding of the pathogenetic mechanisms of mitochondrial forms of hearing loss.

The GJB2 (Cx26) gene pathogenic variants are associated with autosomal recessive deafness type 1A (DFNB1A, OMIM #220290). Direct sequencing of the GJB2 gene among 165 hearing-impaired individuals living in the Baikal Lake region of Russia identified 14 allelic variants: pathogenic/likely pathogenic-nine variants, benign-three variants, unclassified-one variant, and one novel variant. The contribution of the GJB2 gene variants to the etiology of hearing impairment (HI) in the total sample of patients was 15.8% (26 out of 165) and significantly differed in patients of different ethnicity (5.1% in Buryat patients and 28.9% in Russian patients). In patients with DFNB1A (n = 26), HIs were congenital/early onset (92.3%), symmetric (88.5%), sensorineural (100.0%), and variable in severity (moderate-11.6%, severe-26.9% or profound-61.5%). The reconstruction of the SNP haplotypes with three frequent GJB2 pathogenic variants (c.-23+1G>A, c.35delG or c.235delC), in comparison with previously published data, supports a major role of the founder effect in the expansion of the c.-23+1G>A and c.35delG variants around the world. Comparative analysis of the haplotypes with c.235delC revealed one major haplotype G A C T (97.5%) in Eastern Asians (Chinese, Japanese and Korean patients) and two haplotypes, G A C T (71.4%) and G A C C (28.6%), in Northern Asians (Altaians, Buryats and Mongols). The variable structure of the c.235delC-haplotypes in Northern Asians requires more studies to expand our knowledge about the origin of this pathogenic variant.

Митохондриальные формы потери слуха составляют не более 1–2% среди всех несиндромальных случаев тугоухости и глухоты. Одним из наиболее распространенных каузативных вариантов митохондриального генома является m.1555A>G гена MT-RNR1, который ассоциирован с формой глухоты, индуцируемой антибиотиками аминогликозидного ряда (OMIM:561000). В настоящее время вклад данной митохондриальной формы глухоты в этиологию потери слуха остается недостаточно изученным, поскольку детекция m.1555A>G гена MT-RNR1 входит не во все протоколы исследований. В настоящей работе методом ПЦР-ПДРФ анализа с последующим секвенированием по Сэнгеру впервые был проведен поиск патогенного варианта m.1555A>G гена MT-RNR1 у 165 пациентов с нарушениями слуха в Республике Бурятия. В результате, вариант m.1555A>G гена MT-RNR1 в состоянии гомоплазмии был обнаружен у 21 из 165 обследованных пациентов. Общий вклад m.1555A>G гена MT-RNR1 в этиологию нарушений слуха в Бурятии составил 12,7%, при этом высокая доля m.1555A>G гена MT-RNR1 выявлена у пациентов бурятов (20,2%) по сравнению с русскими пациентами (1,3%). Генетико-эпидемиологический анализ идентифицированной митохондриальной формы потери слуха в Бурятии выявил ее повышенную распространенность в трех районах на юге Республики, с максимальным накоплением в Джидинском муниципальном районе (4,5 на 10000). Анализ мировой распространенности варианта m.1555A>G гена MT-RNR1 среди 43435 пациентов с нарушением слуха показал, что его доля составляет в среднем 1,9%. Полученные результаты о высоком вкладе m.1555A>G гена MT-RNR1 в этиологию тугоухости и глухоты у пациентов бурятов свидетельствуют о том, что в регионе озера Байкал нами обнаружен один из наиболее крупных мировых очагов накопления митохондриальной формы потери слуха, который, вероятнее всего, обусловлен эффектом основателя. Mitochondrial forms of hearing loss account for no more than 1-2% among all non-syndromic cases of hearing loss. However, one of the most common causative variants of the mitochondrial genome is m.1555A>G of the MT-RNR1 gene, which is associated with a deafness induced by aminoglycoside antibiotics (OMIM:561000). Currently, the contribution of the mitochondrial deafness to the etiology of hearing loss remains insufficiently studied, since the detection of the m.1555A>G of the MT-RNR1 gene is not included in all research protocols. In this work, using PCR-RFLP analysis followed by Sanger sequencing, the pathogenic variant m.1555A>G of the MT-RNR1 gene for the first time was searched in 165 hearing impaired patients in the Republic of Buryatia. As a result, the m.1555A>G of the MT-RNR1 gene in the homoplasmic state was detected in 21 out of 165 studied patients. The total contribution of the m.1555A>G (MT-RNR1 gene) to the etiology of hearing impairment in Buryatia was 12.7%. At the same time, a high proportion of m.1555A>G of the MT-RNR1 gene was detected in Buryat patients (20.2%), compared to Russian patients (1.3%). A genetic-epidemiological analysis of the identified mitochondrial form of hearing loss revealed its increased prevalence in three south districts in the Republic of Buryatia, with the maximum accumulation in the Dzhidinskii district (4.5 per 10,000 peoples). The analysis of the global prevalence of the variant m.1555A>G of the MT-RNR1 gene among 43435 patients with hearing impairment showed that its share is on average 1.9%. The results obtained on the high contribution of the m.1555A>G to the etiology of hearing impairment in Buryat patients indicate that we have found in the Baikal Lake region one of the largest of the world accumulation of the mitochondrial forms of hearing loss with most likely due to founder effect.

There are different hypotheses on the origin and time of appearance of Russian settlements in the northeast of the Arctic. To study the history of the formation of northern old-settler population of Yakutia, Y-chromosome lineages were traced in representatives of the three groups of residents of the settlement of Russkoe Ust’ye, located in the delta of the Indigirka River (“Pomors,” “Cossacks” and “Zashivertsy”), comparable with the main migration waves of Russian arrival to the Arctic coast of Eastern Siberia. For the first time, the characteristic features of the genetic structure of Russkoustinian population are described based on the data of genome-wide analysis of 740 000 SNPs. The results of the study are more in favor of the “Pomor” hypothesis of the origin of Russkoustinians.

Патогенные варианты гена SLC26A4 ассоциированы как с аутосомно-рецессивной глухотой 4 типа (DFNB4, OMIM #600791), так и с синдромом Пендреда (PS, OMIM #274600). В настоящей работе проведен поиск каузативных вариантов гена SLC26A4 и анализ его генетического окружения (гаплотип CEVA) у шести пациентов из Бурятии с нарушениями слуха и расширенным водопроводом преддверия (EVA), которые в части случаев были сочетаны с кистозными аномалиями улитки (IP-1 и IP-2) и с нарушением тиреоидной функции. Исследование включало клинико-аудиологический анализ порогов слуха, компьютерную томографию височных костей, анализ гормонов гипофизарно-тиреоидной системы (ТТГ, св.Т3 и св.Т4), прямое секвенирование по Сэнгеру кодирующих районов гена SLC26A4 (21 экзон) и генотипирование 12 SNP-маркеров, составляющих гаплотип CEVA. В целом, у обследованных пациентов доля SLC26A4 биаллельных (M2) и моноаллельных случаев в сочетании с CEVA-гаплотипом в транс-положении (M1+CEVA) составила 83,3% (5 из 6 пациентов). При этом, у пациентов бурятов доля случаев с M2 составила 100% (3 из 3 пациентов), в то время как у русских пациентов доля случаев с М2 и М1+CEVA составила 66,6% (2 из 3 пациентов). Высокий мутационный вклад гена SLC26A4 у пациентов бурятов может быть связан с распространенностью в регионе озера Байкал мажорных вариантов этого гена c.919-2A>G (IVS7-2A>G) и c.2027T>A p.(Leu676Gln), характерных для ряда регионов Сибири и Восточной Азии. Идентификация гаплотипа CEVA в транс-положении у одного русского пациента с моноаллельным вариантом гена SLC26A4 (М1+CEVA), свидетельствует об актуальности дальнейшей оценки диагностической значимости CEVA-гаплотипа в когортах российских пациентов с нарушениями слуха. Pathogenic variants of the SLC26A4 gene are associated with both autosomal recessive deafness type 4 (DFNB4, OMIM #600791) and Pendred syndrome (PS, OMIM #274600). In this work, we searched for causative variants of the SLC26A4 gene and its genetic background (CEVA haplotype) in six patients in Buryatia with hearing impairments and an enlarged vestibular aqueduct (EVA), which in some cases was combined with cystic cochlear anomalies (IP-1 and IP-2) and with impaired thyroid function. The study included clinical and audiological analyses of hearing thresholds, computed tomography of the temporal bones, analysis of hormones of the hypothalamic– pituitary–thyroid axis (TSH, free T3 and free T4), direct Sanger sequencing of the coding regions of the SLC26A4 gene (21 exons) and genotyping of 12 SNPs markers of the CEVA haplotype. In general, among the studied patients, the proportion of SLC26A4 biallelic (M2) and monoallelic cases in combination with the CEVA haplotype in trans-position (M1+CEVA) was 83.3% (5 of 6 cases). At the same time, in Buryat patients, the proportion of cases with M2 was 100% (3 out of 3 cases), while in Russian patients, the proportion of cases with M2 and M1 + CEVA was 66.6% (2 out of 3 cases). The high contribution of the SLC26A4 gene in Buryat patients may be associated with the prevalence of the major variants of this gene c.919-2A>G (IVS7-2A>G) and c.2027T>A p.(Leu676Gln) common for regions of Siberia and Eastern Asia. Identification of the CEVA haplotype in trans-position in one Russian patient with a monoallelic variant of the SLC26A4 gene (M1+CEVA) indicates the relevance of further assessment of the diagnostic significance of the CEVA haplotype in cohorts of Russian patients with hearing impairments.

Prostaglandin E2 may be involved in an increase in body temperature during cold stress by the type of fever. At the same time, a significant part of heat production is produced during shivering thermogenesis, due to arbitrary muscle activity, which is accompanied by the release of the hormone irisin. Prostaglandin E2 is formed from arachidonic acid by the enzyme cyclooxygenase-2, which is encoded by the PTGS2 gene. The transcriptional activity of the PTGS2 gene depends on its allelic variants, which can affect thermoregulation processes in different ways. In this regard, the aim of this study is to analyze the polymorphism rs689466 of the PTGS2 gene with the level of irisin in blood plasma in a population of Yakuts living in cold climatic conditions. The study involved 183 women and 80 men (average age 19.73 +/- 1.99 years). Analysis of the association of polymorphism rs689466 of the PTGS2 gene with irisin levels showed that in men with the TT genotype, irisin levels (8.2 +/- 1.85 mu g/ml) were statistically significantly higher (U=261; p=0.005), compared with men with CT+CC genotypes (7.1 +/- 1.25 mu g/ml). In addition, it was found that men with the TT genotype (63.6 +/- 6.67 kg) had a lower weight than men with the CT+CC genotypes (67.93 +/- 7.28 kg; U=279; p=0.01). The detected association of the TT rs689466 genotype of the PTGS2 gene with elevated irisin levels and with a lower weight in men may indicate the effect of prostaglandin E2 on shivering thermogenesis during cold stress, which may play a role in human adaptation to a cold climate.

There are various hypotheses on the origin and time of the appearance of Russian settlements in the Arctic Ocean shores of Eastern Siberia. In order to study the history of the formation of the russian old-settlers of Yakutia, we analyzed the lineages of the Y-chromosome in three groups of residents of the village of Russkoye Ust’ye, located in the delta of the Indigirka River (“Pomors”, “Cossacks” and “Zashivertsy”), comparable with the main migration waves of settlement of Russians on the Arctic coast of Eastern Siberia. For the first time, the characteristic features of the genetic structure of the population of Russkoustinans are described by the data of a genome-wide analysis of 740,000 single nucleotide polymorphisms. The results of the study to a greater extent testify in favor of the “Pomor” hypothesis of the origin of the Russkoustinians.