[Features of the metabolism of polyunsaturated fatty acids in type 2 diabetes mellitus].

Type 2 diabetes mellitus (T2DM) is a widespread disease with a high risk of cardiovascular complications, disability and mortality. The progression of T2DM is closely related to lipid metabolism disorders, caused both by insufficient intake of polyunsaturated fatty acids (PUFAs), and by a violation of their endogenous metabolism. Desaturase enzymes, FADS1/2, are involved in the regulation of PUFA metabolism. Violation of the functioning of FADS1/2 and their genes leads to a change in the biosynthesis of PUFAs and the fatty acid composition of cell membranes. The purpose of this research was to summarize the data of modern literature on the metabolism of PUFAs and the effect of FADS genetic variants on the fatty acid composition of cell membranes in T2DM. Material and methods. The search and analysis of publications was carried out using the PubMed, MEDLINE, Web of Science databases, mainly for the last 10 years, using the search keywords: polyunsaturated fatty acids, fatty acid desaturases, desaturase genes, type 2 diabetes mellitus. Results. In the pathogenesis of T2DM and its complications, many factors play a role, including impaired PUFA metabolism. A large evidence base has been accumulated on the effect of PUFAs on cardiometabolic risk factors in T2DM. The effect of desaturase activity on the fatty acid composition of cells was identified as the most important link in the metabolism of PUFAs. Focusing on the modulation of desaturase activity and studying the polymorphism of fatty acid desaturase genes may be a useful therapeutic option in the treatment of patients with T2DM and its complications. Conclusion. A promising direction of scientific research in the treatment and prevention of T2DM and its complications is the study of genetic mechanisms associated with the metabolism of PUFAs and their metabolites.

[Clinical aspects of the effectiveness of metformin therapy in combination with a low-calorie diet in patients with type 2 diabetes mellitus with various variants of the TCF7L2 gene polymorphism].

The TCF7L2 gene is one of the new markers associated with the development of type 2 diabetes mellitus (DM). Evaluation of the effect of TCF7L2 gene polymorphisms on the effectiveness of hypoglycemic therapy will allow an individual approach to the choice of methods for treating type 2 DM in their carriers. The aim of the research was to study the effect of carriage of TCF7L2 gene polymorphisms on glycemic control parameters in patients with type 2 DM receiving metformin glucose-lowering therapy in combination with a low-calorie version of the standard diet. Material and methods. The study included 55 patients with type 2 DM (mean age 59.9±6.9, BMI 44.3±8.2 kg/m2) receiving metformin monotherapy at a dosage of 1500-2000 mg/day in combination with a low-calorie variant of the standard diet (1730±130 kcal/day). The frequency of occurrence of polymorphisms rs7903146/rs12255372 of the TCF7L2 gene was studied. The indicators of glycemic and metabolic control, anthropometric parameters and body composition were evaluated. Results. The frequency of occurrence of the T-allele of both single nucleotide polymorphisms rs7903146 and rs12255372 of the TCF7L2 gene among patients was 38.2%. Among carriers of the T-allele rs7903146 of the TCF7L2 gene, 72% of patients responded to therapy, showing a statistically significant decrease in the level of fasting glycemia by an average of 16.2±1.6% from the baseline, while among carriers of the CC genotype - 10.5±1.5% (p=0.017). There were no statistically significant changes in glycemic control indicators on hypoglycemic therapy during 7 months of observation, both in the group of T allele and CC genotype carriers. Conclusionss. An improvement in glycemic control was established in patients with type 2 DM among carriers of the T allele rs7903146 of the TCF7L2 gene during metformin therapy in combination with a low-calorie standard diet. The study of TCF7L2 gene polymorphism in combination with indicators of glucose metabolism makes it possible to predict the effectiveness of hypoglycemic therapy with great accuracy.

[Assessment of the sufficiency of Moscow population with folic acid, depending on the combined effect of polymorphism of MTHFR and FTO genes].

The results of assessing the sufficiency of folic acid of the residents of the Moscow region have been presented depending on rs1801133 MTHFR gene polymorphism and rs9939609 FTO gene polymorphism. A total of 326 people were examined, including 74 men and 252 women aged 20 to 65 years. The results of determining the level of folic acid in blood serum showed insufficiency of this vitamin among the population of the Moscow region of the Russian Federation. The expressed vitamin deficit (level <3,0 ng/ml) was detected in 24.2% of the surveyed residents, in 22.8% folic acid level was at the lower bound of the norm (3.0-4.5 ng/ml). The results of genotyping showed a statistically significant association of low folic acid level with rs1801133 MTHFR gene polymorphism in carriers of A allele of rs9939609 FTO gene polymorphism both in the homozygous state (genotype AA) and in the heterozygous (genotype AT) state, OR=4.26; CI (1.40-12.9), p=0.008, as well as with rs9939609 FTO gene polymorphism in carriers of the T allele of rs1801133 MTHFR gene polymorphism both in the homozygous (genotype TT) and heterozygous (CT genotype) state, OR=3.29; CI (1.07-10.1), p=0.03. In carriers of 3 alleles of risk of folic acid deficiency [rs9939609 FTO gene polymorphism and rs1801133 MTHFR gene polymorphism (genotypes CT/AA and TT/AT)] blood serum level of folic acid was below the norm, that indicated folate deficiency in this category of persons.

[The study of rs11801197 polymorphism of the calcitonin receptor gene (CALCR) in Moscow women and children with different level of bone strength].

The frequency of the polymorphism rs11801197 of calcitonin receptor gene (CALCR) was studied by real-time PCR in 422 Moscow women and children, including pregnant women (n=96), lactating (n=29) and non-pregnant women (n=28) and children (n=269) of preschool (2-6 years, n=76) and school age (7-16 years, n=193) with different levels of bone strength (BS) as determined by ultrasound densitometry. It was found that the decrease in the value of the BS (Z-score<-1) was observed in 60% of women, 54% of preschool children and 48% of school children. In the cohort studied the predominant genotype of rs11801197 polymorphism of CALCR gene was CT (38%), the frequency of the genotypes CC and TT - 31%, C and T allele - 50%. There was statistically significant association of BS reduction risk with a C allele of rs11801197 polymorphism of CALCR gene in all examined women (QR=2.034, p=0.02). A positive but not statistically significant association of BS reduction risk with C allele of polymorphism in non-pregnant and pregnant women was found (OR=6.905, p=0.09 and OR=1.902, p=0.09 respectively). The same tendency was observed in preschool children (OR=1.880, p=0.104). In school-aged children C allele was not associated with the risk of BS reduction (OR=0.866, p=0.595). Thus, the allele C is the risk allele of BS reduction. The frequency of CC genotype in Moscow women is much higher than that in women in Europe and in women of North-West region of Russian Federation. Women in the Moscow region - the carriers of rs11801197 polymorphism of CALR - gene need in personalized support of their bone health.

[The study of the association between rs2228570 polymorphism of VDR gene and vitamin D blood serum concentration in the inhabitants of the Russian Arctic].

Genetic factor plays a significant role in nutrient deficiency development, including vitamins, by present time the association between several genetic polymorphisms and vitamin deficiency in the different regions of the world has been established. The aim of this study was to evaluate the possible association between VDR FokI polymorphism and vitamin D sufficiency in the population of the Yamal-Nenets Autonomous District of the Russian Federation. The group of participants included 172 people, among them 133 women and 39 men aged 20 to 75 years old. Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism (SNP) of FokI T/C: (rs2228570) using allele-specific amplification, results were detected in real time using TaqManprobes complementary DNA polymorphic sites. The concentration of 25-hydroxyvitamin D [25(OH)D] was measured by ELISA. The decreased level of 25(OH)D in blood serum (<20 ng/ml) occurred in 38.2% of the population surveyed, and 25(OH)D blood level in the alien population of the region was significantly lower than that in the indigenous population. Genetic peculiarities of the inhabitants of the Arctic zone were identified by comparison with the inhabitants of the European part of the Russian Federation. Allele C frequency of VDR rs2228570 polymorphism in the alien population was 71.1%, higher than in indigenous population (50.0%) while in the inhabitants of the European part of Russia it was 57.8%. Vitamin D blood level was statistically significantly lower in all homozygous C allele carriers than in genotype TT carriers, and vitamin D deficit frequency was 2.3 fold higher (48.4 vs. 21.1%, p<0.05). In the group of indigenous people of this region vitamin D levels in carriers of CC and CT genotype were also significantly lower than that of TT genotype carriers. The incidence of vitamin D deficiency in homozygous carriers of the allele C (45.5%) was 5.5 fold higher than among TT genotype carriers (p<0.01), and 1.6 fold higher than that in CT genotype carriers (p>0.05). Thus, the association between C allele presence of rs2228570 polymorphism of VDR gene and a deficiency of vitamin D (reduced levels of 25 (OH)D in blood serum) has been revealed.

[Assessment of efficiency of the personalized therapy of patients with obesity and diabetes mellitus 2 types appointed on the basis of studying rs5219 polymorphism of KCNJ11 gene].

The aim of the study was to develop and evaluate the effectiveness of personalized therapy forpatients with diabetes mellitus type 2 (DM) and obesity based on the study of rs5219 polymorphism of KCNJ11gene. The study involved 120 women with DM and obesity I-II degree. Genotyping was performed in patients using allele-specific amplification with the detection in real time. Depending on the genotype of KCNJ11 gene patients with DM and obesity received different treatment and were divided into 2 groups (40 patients in each): group A (C/T genotype) received standard low-calorie diet + metformin 2000 mg/day and group B (T/T genotype) received a personalized diet + vitamin-mineral complex (VMC) + metformin 2000 mg/day. Results of the study of rs5219 polymorphism of KCNJII gene in patients with,DM and obesity have shown that 49% of them were carriers of the mutated T allele in the heterozygous form and 37% - in the homozygous variant. It has been found that reducing of calories in a diet promoted weight loss in patients with DM and obesity mainly due to lean body mass in Group A and in Group B - mainly due to the fat component. A significant decrease in blood glucose under complex therapy was observed in both groups. However, after treatment in group B blood glucose levels were significantly lower than in group A. Thus, personalized therapy of patients with DM and obesity should be based on molecular genetic studies that will allow to improve the efficiency of therapeutic measures in these diseases.

[The investigation the combined effect of SNP rs9939609 (gene FTO) and rs4994 (gene ADRB3) polymorphisms on risk of obesity].

The genetic factor plays a significant role in the development of obesity, by present time the association of hundreds genetic polymorphisms with the risk of this disease is established. However, the combined influence of genetic polymorphisms remains practically unstudied. We aimed to investigate the combined effect SNP rs9939609 (gene FTO) and rs4994 (gene ADRB3) polymorphisms on risk of obesity. A case-control study was conducted, including255 obese case (BMI>30 kg/m2) and 427 non obese controls (BMI<30 kg/m2). Genotyping was performed using allele-specific amplification, detection results in real time using TaqMan-probes complementary DNA polymorphic sites. It has been shown, that presence of one mutant allele of rs9939609 (gene FTO) and rs4994 (gene ADRB3) leads to statistically significant association with obesity. Presence of two mutant alleles in different polymorphic variants increases risk of obesity by 15%, presence of three mutant alleles - by 2.63 fold. The quantity surveyed, suffering obesity, increased depending on the number of mutant alleles in studied genetic polymorphisms. Presence of one or two mutant alleles in one polymorphic variant increased the number of patients with obesity by 13.4%, presence of two or three mutant alleles in different polymorphic variants -by 18-19%.

[The association of genetic polymorphisms with non-communicable disease among Arctic population].

The review analyzed genetic polymorphisms contribute to the development of non-communicable diseases among the inhabitants of the Arctic. It is known that the area belongs to the arctic areas of discomfort for living and employment rights. Ecological features of the Far North have contributed to the adaptation of the indigenous population to environmental conditions, which manifested itself in particular in the power features that provide a low prevalence of obesity, metabolic syndrome, type 2 diabetes and cardiovascular disease. Active development of the Arctic zone and the associated lifestyle changes in the population, including the nature of power, caused a change in the prevalence and trends of non-communicable diseases, which has its own characteristics in comparison with the ethnic groups living in more southern latitudes. These features, as follows from the results of a number of studies to be associated, including the presence of genetic polymorphisms characteristic of the population of the Arctic zone.

[The study of energy balance in individuals with the Trp64Arg polymorphism of the ß3-adrenoreceptor gene].

The study involved 104 people living in the Moscow region, including 18 men and 86 women aged 18 to 67 years. Genotyping of rs4994 ADRB3 polymorphisms was performed using allele-specific amplification, with result detection in real time and using TaqMan-probes complementary to polymorphic DNA regions. The frequency of the mutant allele in individuals was 8.0%, while the Trp64Trp genotype was detected in 84.0% of cases, Trp64Ar - in 16.0%, AA - in 19.0%. Compared with men with genotype Trp64Trp, the men with the Trp64Ar polymorphisms (rs4994) of ADRB3 gene had significantly lower energy expenditure at rest value, calculated per kg of body muscle mass that was associated with higher fat mass, levels of blood serum leptin and LDL cholesterol. The data obtained suggested that leptin could be a possible intermediary contributing to the association between the rs4994 polymorphism of ADRB3 gene and energy disbalance.

[The study of the association of polymorphism rs659366 gene UCP2 c obesity and type 2 diabetes among residents of the Moscow Region].

1112 people from Moscow region have been surveyed. Genotyping of rs659366 polymorphism UCP2 gene was performed using allele-specific amplification, result detection in real time and using TaqMan-probes complementary DNA polymorphic sites. The study of rs659366 polymorphism of the UCP2 gene has showed that 36.9% of patients had genotype AA, 46.7%--genotype AG, and 16.5%--genotype GG. The frequency of allele A was 60.2%, allele G--39.8%. BMI, value of fat mass, visceral fat area, serum glucose and triglyceride levels were significantly higher in carriers of A allele in the homozygous and heterozygous state than in carriers of G allele in the homozygous state. Frequency of A allele compared with G allele in obese patients (BMI greater than 30 kg/m2) was: OR--1.52; CI (1.24-1.86), p = 0.001, and in diabetes mellitus type 2--OR--1.22; CI (0.910-1.622), p = 0.19.

[The study of the association of polymorphism rs5219 gene KCNJ11 with obesity and the risk of type 2 diabetes among residents of the Moscow Region].

The study involved 1,050 people living in the Moscow region, including 311 men and 739 women. Genotyping of KCNJ11 rs5219 polymorphisms was performed using allele-specific amplification, result detection in real time and using TaqMan-probes complementary to polymorphic DNA regions. Results of the study of KCN11 rs5219 gene polymorphism showed that 14.2% of the patients had TT genotype, 44.8%--CT genotype, 41.0%--CC genotype. The frequency of the mutant T alele was 36.6%, C allele--63.4%. The frequency of the T allele didn't significantly differ in individuals with obesity (BMI ≥ 30 kg/m2) and individuals with a BMI < 30 kg/m2 (38.8% and 35.7%, respectively), OR--1.14; CI (0.907-1.439), p = 0.26. At the same time, the amount of energy expenditure at rest, calculated per kg lean body weight, and serum content of uric acid in were significantly higher in individuals with KCNJ11 rs5219 polymorphism, both in homo-, and in the heterozygous type. The frequency of the T allele and TT genotype in patients with hyperglycemia was higher than in the comparison group. Genotype TT is associated with type 2 diabetes (OR = 2.35, CI: 1.018-5.43, p = 0.04).

[The study of rs1800012 polymorphism of the alphal-chain collagen type 1 gene in Moscow women and children with different level of bone strength].

The frequency of rs1800012 polymorphism of alpha1-chains of type 1 collagen gene (COL1A1) was studied by real-time PCR in 422 Moscow women and children, including pregnant women (n=96), lactating (n=29) and non-pregnant women (n=28) and preschool children (2-6 years, n=76) and school children (7-16 years, n=193) with different levels of bone strength (BS) as determined by ultrasound densitometry. It was found that the decrease in the value of the BS (Z-score < -1) was observed in 60% of women, 54% of preschool children and 48% of school-aged children. In the surveyed cohort the predominant genotype of rs1800012 polymorphism CO1A1 geneI gene was GG (55.1%), the frequency of the genotype TT--7.6%, of T-allele--26.2%. There were no statistically significant relationships of BS with a particular genotype of rs1800012 polymorphism 1f1COLIAI gene in all examined women. A positive but not statistically significant association of T allele with a risk BS reduction was found in non-pregnant and pregnant women (OR=2.143, p=0.31 and OR=1.227, p=0.55, respectively). For preschool and school-aged children T allele was not associated with the risk of BS reduction. In school-age children a statistically significant inverse association of T allele with the risk of BS reduction was shown (OR=0.621 wth

[The study of the peculiarities of metabolism in individuals with rs9939609 polymorphism of FTO gene].

A total of 104 people, among them were 18 men and 86 women aged 18 to 67 years--people in the Moscow region of the Russian Federation, in the sanatorium treatment. Association embodiment rs9939609 FTO obesity was studied using allele-specific amplification, detection results in real time using TaqMan-probes complementary DNA polymorphisms. The frequency of the mutant allele in individuals was 47.0%, while the TT genotype was detected in 25.0% of cases, AT--in 56.0%, AA.0%. In men, prevalence rates of obesity risk allele (A) is higher than in women. In individuals with obesity (BMI over 30 kg/m2) indicated the presence of more AA genotypes (2 7.8%) compared to individuals with a body mass index of less than 30 kg/m2 (14.1%) and a high frequency of occurrence (54.2 versus 43.0%) risk allele A. Compared with individuals with genotype TT, the examinees with the AA genotype rs9939609 FTO gene was significantly higher BMI, waist circumference, hip circumference, fat mass. The same patients energy expenditure at rest value, calculated per kg of lean body mass or muscle, was slightly less than with TT genotype. In individuals with the AA genotype rs9939609 FTO gene compared with the TT genotype had significantly lower levels of HDL cholesterol and serum iron in the background significantly elevated concentrations of uric acid. Thus, the evaluation of patients with the use of innovative technologies in a spa treatment allows their personal alimentary correction for the prevention and treatment of non-communicable diseases.

[The role of the Consultative and Diagnostic Centre "Healthy Nutrition" in the diagnosis and nutritional prevention of non-communicable diseases].

In a consultative and diagnostic center "Healthy Nutrition" of Institute of Nutrition the nutritional status of 3500 patients (mean age 48.4 ± 0.3 years) liv- ing in the Moscow region, using a system Nutritest IP-3, including genomic analysis has been examined. In the analysis of dietary intake by an average review, increased energy intake due to excess intake of the total (44.2% energy) and saturated fat (13.6%) has been shown. 30.0% of patients were overweight and 34.1% were obese. Osteopenia was detected in 31.0% of men and 25.0% women, osteoporosis--20.9% and 30.3%, respectively. Analysis of the results of biochemical studies revealed increased cholesterol in 68.7% of patients, LDL cholesterol--at 63.9%, triglycerides-- at 22.5%, glucose--at 29.4%. The frequency of the occurrence of risk alleles of genes associated with the development of obesity and type 2 diabetes mellitus was: 47.8%--for the polymorphism rs9939609 (FTO gene), 8.3%--for polymorphism rs4994 (gene ADRB3), 60.2%--for the polymorphism rs659366 (gene UCP2), 36.6%--for the rs5219 polymorphism in the gene of ATP-dependent potassium channel.