Prevalence of Trehalase Enzymopathy Genetic Determinants in Siberian and Russian Far East Populations.

To date, it has been established that the patient's genotype plays a significant role in the formation of trehalase enzymopathy: the level of enzyme activity decreases when the G→A allele replacement occurs in the rs2276064 locus of the TREH gene. To assess the prevalence of trehalase deficiency, extensive population-based studies are needed. Clinical observations show that the reduced activity of bowel trehalase is more common in the Arctic than in European populations. The aim of this research was to analyze the frequency of the alleles and variants of trehalase gene (rs2276064 TREH) in the indigenous small-numbered populations of Siberia and the Russian Far East. MATERIALS AND METHODS: . Using the Infinium iSelect HD Custom BeadChip biochip (Illumina, United States) on the iScan platform and real-time polymerase chain reaction on a Bio-Rad CFX96 Touch amplifier, genotyping of 1068 DNA samples was carried out, of which 667 represent 10 ethnic groups of the indigenous people of the North of Siberia and the Far East of the Russian Federation. Two reference groups (357 samples) of Russians (n = 311) and Yakuts (n = 46) represent the "Caucasoid" and "Mongoloid" poles of the Russian population. RESULTS: : The reduced trehalase activity that the heterozygous GA*TREH genotype determines can manifest itself in 19.8-53.7% of indigenous northerners. An additional 1.0 to 19.7% of the population are carriers of the AA*TREH genotype, which is associated with apparent trehalose malabsorption. The carriers may experience nausea, abdominal pain, and other dyspeptic symptoms after eating trehalose containing foods. The total risk of trehalase enzymopathy among the indigenous northerners in the Asian part of the Russian Federation is very high and can reach 60-70%. There is a gradient in the A*TREH allele frequencies in the small-numbered indigenous northern groups of Russia from the west (Khanty, Mansi, Nenets) to the east (peoples of the Far East). CONCLUSIONS: : The results are consistent with previously reported data on the higher carriage of the A*TREH mutant allele in Mongoloid populations compared to Caucasoid groups. It was hypothesized that, while the initial A*TREH allele prevalence in Mongoloid groups was moderately high, an adaptation to a low-sugar protein-lipid "high-latitude" diet led to a weaker control over the maintenance of the carriage of the ancestral G* allele. Trehalose malabsorption requires special attention of specialists in the field of nutrition, gastroenterology, public health, and medical genetics working in high-latitude regions.

[Genetics of sucrose metabolism disorders in different population groups].

The study of the genetic determinants of the disaccharidase activity opens up new prospects for improving diagnostics and choosing medical tactics in gastroenterology. The aim of the study was to systematize the data on the role of the sucrase-isomaltase gene (SI) in regulating sucrose metabolism and the contribution of SI mutations to the prevalence of sucrose malabsorption disorders (sucrase-isomaltase deficiency, SID) and certain forms of enterological pathology in different population groups. Material and methods. A review of the peer-reviewed scientific literature, mainly in the PubMed database (https://pubmed.ncbi.nlm.nih.gov) and eLibrary (https://elibrary.ru), was conducted using key words: carbohydrate malabsorption, sucrase, sucrase-isomaltase deficiency, sucrase-isomaltase SI gene. The search depth was not specified, but particular attention was paid to recent publications. The gnomAD database (https://www.ncbi.nlm. nih.gov/snp/rs781470490) was also used. Results. According to the review results, 37 out of 150 known SI gene mutations have been confirmed to contribute to reduced sucrase activity or restricted sucrase production. The prevalence of point mutations in the SI gene is estimated at 0.0006%, but carrier rates of the SI delAG deletion (rs781470490), manifested as homozygosity in SID, are very high (5-21%) in indigenous populations of Arctic regions in East Asia and America. Medicalgenetic research methods improve the accuracy of differential diagnosis of primary and secondary SID and other forms of disaccharide and polysaccharide malabsorption. The formation of databases on the prevalence of genetic determinants of sucrase-isomaltase insufficiency is a promising way to refine the epidemiology of SID. There is an increased (0.2-2.3%) risk of clinical manifestations of SID in homozygous carriers of the SI delAG mutation in the Chukotka, Kamchatka, and Northern Priochotye populations. Verification of reports on a less pronounced tendency to lipid metabolism disorders in SI delAG carriers compared with the control group is recommended. Conclusion. Manifestations of mutant SI variants in the phenotype are associated with the presence of accompanying carbohydrate malabsorption variants and specific gut microbiota. The SI 15Phe variant (rs9290264) may contribute to the development of irritable bowel syndrome.

[The influence of environmental factors on the prevalence of «thrifty genotypes¼ as predictors of metabolic disorders].

"Thrifty genotypes" are the risk factors for obesity and lipid and energy metabolism disorders. Hence, it is important to assess the contribution of environmental factors that influenced the thrifty genotypes' population distribution. Aim of the study - systematization and critical analysis of published data on population variability, relationship with climatic and environmental characteristics, association with traditional types of lifestyles, and nutrition for the «thrifty genotypes¼ of APOE, UCP1, UCP3, and FTO genes. Material and methods. The selection of publications from the last 20-25 years presented in the PubMed database (https://pubmed.ncbi.nlm.nih.gov) was carried out by the keywords of the generalizing rank (thrifty genotype, thrifty phenotype, drifty genotype), then narrowed down to the APOE, UCP, FTO. The final set includes publications that consider the association of genotypes with the ecological conditions of the population. Results. Our analysis of publications has confirmed the ethnic and geographical variability in the allele distribution of APOE, UCP1, UCP3, and FTO genes. However, the nature of this variability hasn't been studied sufficiently; the contribution of individual factors of the natural and anthropogenic environment remains unclear. The information on the geographical distribution of the APOE gene alleles is quite complete, while the data on the «thrifty genotypes¼ of UCP and FTO require further study. Conclusion. The frequency of the UCP1 and UCP3 alleles associated with effective non-contractile thermogenesis is increased in populations adapted to low temperatures. However, the population-geographical pattern of the UCP thrifty genotypes' variability as a determinant of increased fat deposition has been studied insufficiently. The carriage of FTO mutant variants increases the adaptability of groups with a traditional lifestyle and diet but is maladaptive in an urbanized environment. The influence of natural and ecological conditions on the formation of the FTO allele geographical distribution requires more attention. The results obtained allow us to propose the included groups' ranking according to the past environmental management and nutrition will facilitate the search for ecological factors that influenced the geographical distribution of genotypes (and, accordingly, populations with different levels of risk of metabolic disorders).

[Prevalence of trehalase enzymopathy genetic determinants in Siberian and Russian Far East populations].

To date, it has been established that the patient's genotype plays a significant role in the formation of trehalase enzymopathy: the level of enzyme activity decreases when the G→A allele replacement occurs in the rs2276064 locus of the TREH gene. To assess the prevalence of trehalase deficiency, extensive population-based studies are needed. Clinical observations show that the reduced activity of bowel trehalase is more common in the Arctic than in European populations. The aim of this research was to analyze the frequency of the alleles and variants of trehalase gene (rs2276064 TREH) in the indigenous small-numbered populations of Siberia and the Russian Far East. Material and methods. Using the Infinium iSelect HD Custom BeadChip biochip on the iScan platform and real-time polymerase chain reaction on a Bio-Rad CFX96 Touch amplifier, genotyping of 1068 DNA samples was carried out, of which 711 represent 10 ethnic groups of the indigenous people of the North of Siberia and the Far East of the Russian Federation. Two reference groups of Russians (n=311) and Yakuts (n=46) represented the "Caucasoid" and "Mongoloid" poles of the Russian population. Results. The reduced trehalase activity that the heterozygous GA*TREH genotype determines can manifest itself in 19.8-53.7% of indigenous northerners. An additional 1.0 to 19.7% of the population are carriers of the AA*TREH genotype, which is associated with apparent trehalose malabsorption. The carriers may experience nausea, abdominal pain, and other dyspeptic symptoms after eating trehalose containing foods. The total risk of trehalase enzymopathy among the indigenous northerners in the Asian part of the Russian Federation is very high and can reach 60-70%. There is a gradient in the A*TREH allele frequencies in the small-numbered indigenous northern groups of Russia from the west (Khanty, Mansi, Nenets) to the east (peoples of the Far East). Conclusion. The results are consistent with previously reported data on the higher carriage of the A*TREH mutant allele in Mongoloid populations compared to Caucasoid groups. It was hypothesized that, while the initial A*TREH allele prevalence in Mongoloid groups was moderately high, an adaptation to a low-sugar protein-lipid "high-latitude" diet led to a weaker control over the maintenance of the carriage of the ancestral G allele. Trehalose malabsorption requires special attention of specialists in the field of nutrition, gastroenterology, public health, and medical genetics working in high-latitude regions.

[Genetically determined trehalase deficiency in various population groups of Russia and neighboring countries].

Due to the low specificity and sensitivity of non-invasive clinical tests trehalose malabsorption remained out of sight of gastroenterologists. Therefore, the specialists regard this disorder as rare. Trehalose became widely used in the food industry as a harmless sucrose substitute, sweetener and stabilizer. After the discovery of the trehalase gene (rs2276064 TREH), it was found that the A*TREH allele is the determinant of the disaccharide absorption disorders, and the allele's carriership may be high in some groups. There is not enough information on the A*TREH frequency in the population of Russia. The aim of the study was to analyze the allele and genotype frequencies of the trehalase gene (rs2276064 TREH) in the main population groups of the Russian Federation and neighboring countries. Methods. DNA samples from 1146 unrelated subjects belonging to 21 population groups of Russia, Azerbaijan, Tajikistan and Mongolia were genotyped by the two following methods: 1) using the Infinium iSelect HD Custom Genotyping BeadChip (Illumina, USA) on the iScan platform; 2) by the real time polymer-chain reaction (PCR) method on the Bio-Rad CFX96 Touch amplifier. Results. It has been found that on the territory of the Russian Federation the frequency of the A*TREH allele increases from the west to the east. The frequencies are lowest in the groups of Russians and Finns of the Northwest (0.01-0.03), up to 0.07 in the populations of Central Russia and the Volga region, and even higher toward the Southern Urals (Bashkirs 0.15), in the Transurals and Southern Siberia (0.19 in the Altai people, 0.30 in the Tuvinians and Mongols). Up to 1% of the population of the European part of the Russian Federation have the AA*TREH genotype (i.e. trehalose intolerance in phenotype), and up to 15% (GA*TREH genotype) have a reduced ability to absorb the disaccharide. In the Asian part of the country (Siberia, Altai, Baikal) the genotypes carriers constitute up to 12 and 46% respectively. Conclusion. Trehalose malabsorbtion is an underappreciated problem of particular practical importance for regions with high concentrations of indigenous population (Yakutia-Sakha, Buryatia, Tyva, etc.). It would be feasible to consider food labelling of trehalose.

[Nutritional status of children in rural areas of the Komi Republic and Khanty-Mansi Autonomous Okrug - Yugra by anthropometric data].

A characteristic feature of the "global obesity epidemic" in recent decades is the rapid spread of overweight among the rural population. However, there is a lack of objective data on how this process is unfolding in the northern and Arctic regions of the Russian Federation. The aim of the work was to analyze the prevalence of malnutrition and rates of overweight and obesity in children living in Khanty-Mansi Autonomous Okrug - Yugra (KhMAO) and the Komi Republic (KR). Material and methods. We conducted a study of the nutritional status of rural children in the northern regions of the Russian Federation in 2018-2019. The subjects of the study were children aged 3-17 years of KhMAO, ethnic Khanty, Mansi and of various non-indigenous descent in small remote settlements (n=302) and 956 children in the administrative center of the northern district, a town-type residency. We also examined 7-17-year-old children (n=628) in large settlements of the KR, over 90% of them were ethnic Komi. For each individual, body mass index values (BMI) were calculated. The nutritional status was assessed by comparing the individual BMI with the age and sex specific standards set by the Ministry of Health of the Russian Federation (2017). Results and discussion. 74.4% of children aged 3-6 in KhMAO, and 70% of the 7-17-year-old children of KR and KhMAO meet the standards for their age-sex groups; 6.1% of children aged 3-17 are underweight and 19.5% are overweight. Among the 7-17-year-olds, the ratio of the underweight and overweight (including obese) differs significantly in the settlement dwellers of the KR from that in the living in small settlements of KhMAO (p=0.004), as well as in the group of town residents of KhMAO (p=0.017). The children of the KR have slightly higher percentage of the overweight and obese (26.6 vs 25.7 and 24.8% in the town and settlements of KhMAO, respectively), but significantly lower percentage of those who are underweight (1.9 vs 5.0 and 6.8%). The proportion of obese schoolchildren in small remote settlements of KhMAO is higher than that in the large settlements of KhMAO and in large settlements of the KR (13.1, 7.7 and 9.2%, respectively). Conclusion. There were no differences found between ethnic groups, however the role of social and anthropological factors in the formation of the nutritional status differences between the indigenous and non-indigenous children in Western Siberia calls for further investigation.

[Carbohydrate-related nutritional and genetic risks of obesity for indigenous northerners].

By the end of the 2010-s the prevalence of obesity among the indigenous people of the North approached to the all-Russia one and the speed of the spread of other metabolic disorders exceeded the average all-country levels. Aim of this review is to analyze data on the increase in consumption and variety of sugars coupled with a genetic specificity of regulation of saccharidase activity and their possible impact on the matters. Results. It have been shown that the traditional protein-lipid-based northern type diet has substantially changed and now contains a high proportion of carbohydrates. The carbohydrate per capita consumption among the indigenous people of the North has reached the all-Russia average level (40 kg per year) which exceeds the European average of 36.2 kg per year. The variety of food disaccharides has also considerably increased. The daily consumption of sucrose, at the beginning of the 20th century it was the only sugar contained in the store-bought foods, increased from 30 g in the 1930s to 63-65 g in the 1990s. In addition, the proportion of sucrose dropped to 60-70 per cent, while the contribution of other disaccharides (lactose, trehalose) reached 30-40 per cent. Daily starch consumption has also increased and got close to the national average (males 228.5 g, females 157.5 g per day). Such a diet in itself increases the risk of metabolic disorders and obesity. The high prevalence of the genotypes that determine reduced levels or inability to produce sucrase-isomaltase, lactase, trehalase, salivary and pancreatic amylases among northerners becomes a negative cofactor. The evolutionary driven and embodied in genotype reduced ability of the indigenous Arctic people to digest complex carbohydrates is in a conflict with the growing consumption of sugars and starchy foods in modern conditions. The northern people have a high proportion of carriers of the AG deletion in SI gene (3.5-14.3% against 0.05-0.2% among Europeans) which determines malabsorption of sucrose. The CC/LCT genotype (96.6% in northerners, 36-49% in Russians) presumes lactose intolerance and is associated with the risk of childhood obesity. The occurrence of A allele in the rs2276064 locus of TREH gene (trehalose intolerance; 31.3-58.9% in northerners, 1.9% in Europeans) increases the probability of the onset of type 2 diabetes mellitus. According to preliminary estimates, 28-52% of the northerners completely lost AMY gene that precludes or drastically reduces the ability to digest starch. A reduction in the number of copies of AMY gene (the average number of copies AMY2A - 4, in, in northerners it is 1.0-1.4) is associated with overweight and obesity. Conclusion. The analysis shows that, in the case of the modern indigenous northerners, nutritional and genetic risks of metabolic disorders accumulate.

[Anthropometric indicators of physical development and nutritional status employed in hygiene practice in Russia].

In the current review, we consider the main working methods of Russian hygienists to assess anthropometric indices using a) regional data on (populational) variability of the concerning measurements and b) unified reference data applicable in most regions. An analysis showed that in most cases, the regional standards are based on average values and variabilities derived from a local sample, which can not serve as a working normative. As a result, these so called "standards" do not provide information on how healthy children should develop, and the assessments inferred are difficult to integrate to draw a picture for the whole country. In 2017, the Ministry of Health of the Russian Federation recommended the use of the WHO Child Growth Standards and the WHO Growth Reference for the purpose of medical screenings in children and adolescents. These data sets reflect the conditions, that healthy children should attain growing in supportive environment, with adequate nutrition and care. The single set of criteria will allow unifying the data collected in different regions, which is a necessity in communal hygiene and medical statistics. However, additional research is needed to check the validity of the WHO standards and reference to assess physical development and nutritional status in highly anthropologically specific populations, in particular in those indigenous and long-ago adapted to the sharply continental or Arctic climate.

[Differences in self-assessment of health and psychological wellbeing between healthy and unhealthy young adults].

Self-assessment of health is the one out of the most important characteristics, which gives an idea about the health of the respondent as a psychophysiological continuum. The purpose of this study is to establish the relationship between indices of self-rated health and characteristics of the psychological well-being. Sample 344 young adults - students at an average age of 20.9 ± 1.6 years. Methods. "Self-assessment of health" questionnaire was used; MOSSF36 questionnaire and "Psychological wellbeing scale" developed by K. Riff. Respondents were divided into groups: (1) without chronic diseases; (2) having one or more chronic diseases of any etiology. Results. The presence of chronic diseases was shown to negatively effect on the self-estimation of physical and psychological state. The significant positive correlation (p <0,001) between the perceived health and subjective well-being was found. Healthy individuals perceive the state of their own physical health and psychological wellbeing as unrelated to each other characteristics. In contrast, in cases with even mild chronic health problems there is pronounced the relationship between somatic and psychological health, which forms a complex of physical and psychological factors determining the general state of a person.

[Cortisol as a marker of stress].

The role of cortisol (Crt), dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) in stress responses were shown. The fluctuations in concentration of Crt, DHEA and DHEA-S depending on age, sex and time of the day in norm and under acute and chronic stress were quoted. The main techniques of assessment of serum, urine and saliva Crt concentrations were discussed. A special attention had been paid to the use of Crt concentration in anthropological and psychological research. Bibliography comprises 181 works.