THE ROLE OF FATS REGULATING GENES IN THEDEVELOPMENT OF METABOLIC SYNDROME

ABSTRACT

It is known that impaired lipid metabolism is one of the important factors in the pathogenetic development of metabolic syndrome (MS). Variable environmental factors in disorders of lipid metabolism: non-compliance with dietary rules (in particular, excessive consumption of animal products and low consumption of vegetable oils), smoking, consumption of excessive alcoholic fatty foods and hypodynamics. A constant constant risk factor is the human genome. These variable and non-variable risk factors have been found to co-occur in most cases in the development of MS. This is because various environmental factors can alter the expression of genes in the human genome.

One of the genes involved in lipid metabolism is ADRB2 (Beta-2 adrenergic receptor). The ADRB2 gene was discovered in 1987 by Kobilka and other authors on chromosome 5 - 5q32 (Gln27Glu polymorphism). The ADRB2 gene is composed of 1 exon, 2015 nucleotides, and 413 amino acids. Disorders of lipid metabolism play an important role in the activity of the cardiovascular, pulmonary, digestive, endocrine and central nervous systems. More than 80 polymorphisms of the ADRB gene have been identified, and one of the most common and important polymorphisms is Gln27Glu (rs1042714) (12).

АННОТАЦИЯ

Известно, что нарушение липидного обмена является одним из важных факторов патогенетического развития метаболический синдром (МС). Вариабельные факторы внешней среды при нарушениях липидного обмена: несоблюдение правил питания (в частности, избыточное потребление продуктов животного происхождения и малое потребление растительных масел), курение, чрезмерное употребление алкогольной жирной пищи и гиподинамия. Постоянным фактором риска является геном человека. Было обнаружено, что эти вариабельные и невариабельные факторы риска сосуществуют в большинстве случаев при развитии рассеянного склероза. Это связано с тем, что различные факторы окружающей среды могут изменять экспрессию генов в геноме человека.

Одним из генов, участвующих в метаболизме липидов, является ADRB2 (бета-2-адренергический рецептор). Ген ADRB2 был открыт в 1987 г. Кобилкой и другими авторами на хромосоме 5 - 5q32 (полиморфизм Gln27Glu). Ген ADRB2 состоит из 1 экзона, 2015 нуклеотидов и 413 аминокислот. Нарушения липидного обмена играют важную роль в деятельности сердечно-сосудистой, легочной, пищеварительной, эндокринной и центральной нервной систем. Идентифицировано более 80 полиморфизмов гена ADRB2, и одним из наиболее распространенных и важных полиморфизмов является Gln27Glu (rs1042714) (12).

Keywords: Metabolic syndrome, diabetes, obesity, ADRB2 (rs1042714) Gln27Glu, beta-2adrenergic receptor, lipolytic receptor, allele, frequency, phenotype and genotype.

Ключевые слова: метаболический синдром, сахарный диабет, ожирение, ADRB2 (rs1042714) Gln27Glu, бета-2-адренорецептор, липолитический рецептор, аллель, частота, фенотип и генотип

Introduction

Beta 2 adrenergic receptor is a major lipolytic receptor in the human fat cell. The ADRB2 gene encodes a beta 2-adrenergic receptor bound to a G protein. Various polymorphisms and mutations in this gene are associated with these diseases associated with decreased response to bronchial asthma, obesity, type 2 diabetes, cardiovascular disease, and other B2-adrenergic receptor agonists (1).

When b2-adrenergic receptors are stimulated in the central nervous system, agitation and tremor can lead to the development of mutations in the ADRB2 gene encoding beta-2-adrenergic receptors. The ADRB2 gene, a lipolytic receptor gene in human fat cells, plays a role in lipid mobilization. The literature suggests that the importance of the Gln/Glu polymorphism of the ADRB2 gene in the origin of obesity is due to the fact that the polymorphism of this gene leads to resistance to adrenaline in fat cells and disrupts the lipolysis process. This results in fat accumulation and obesity (2). One of the most common polymorphisms is the Gln27Glu mutation (rs1042714), which occurs as a result of changes in the amino acid sequence at the extracellular N-terminal of the ADRB2 gene. Some studies on this gene show positive associations (3-4), while others show negative results (5-6); indicates In particular, gene polymorphisms encoding the b2-adrenergic receptor (ADRB2) may alter the thermogenic effects of catecholamines associated with obesity and weight recovery (7-8) and also disrupt the lipolysis process (9). Based on the above considerations, we can say that allelic variants of energy-related genes can have a negative effect on fat loss (10) and weight loss (11), and it is clear that the object of this study is more specific evidence need.

Цель: изучить частоту встречаемости полиморфизма rs1042714 генотипа Gln27Glu гена ADRB2 при метаболическом синдроме (ожирении и сахарном диабете).

The aim: To study the frequency of occurrence of ADRB2 gene Gln27Glu genotype rs1042714 polymorphism in metabolic syndrome (obesity and diabetes).

Materials and methods

The study involved 50 patients with metabolic syndrome and 50 conditionally healthy people living in the Republic of Uzbekistan. Patients with Metabolic Syndrome (n = 50) were divided into two subgroups depending on the incidence of the disease. Group A (n = 28) has MS and is composed of obese patients and group B (n = 22) is diabetic.

To determine the rs1042714 polymorphism of the ADRB2 gene Gln27Glu genotype, DNA was isolated from blood leukocytes, followed by analysis of this gene (PCR) using the Sintol test using a rotor gene. The analysis of the results was carried out using the mathematical software package OpenEpi 2009, Version 9.3.

Analysis of the results

During the study, we studied the Gln27Glu polymorphism of the ADRB2 gene. The main and control groups were selected. Initially, a comparative analysis of the distribution rates of allele variants of the ADRB2 gene rs1042714 locus in primary and control group samples showed that the Gln allele was 63% and 76%, respectively, and the Glu allele was 37% and 24%, respectively (ch2 = 3.986; P = 0.046; OR = 1.86; 95% CI 1.008-3.432). It was observed that the prevalence of Glu allele in our main group of patients was higher than in the control group samples and was statistically significant.

Figure 1. Distribution rate of ADRB2 gene rs1042714 polymorphism alleles in baseline and control group samples

Figure 2. Distribution rate of ADRB2 gene rs1042714 polymorphism genotypes in baseline and control group samples

The incidence of the dominant Gln/Gln genotype among the patients in our follow-up was found to be significantly lower than in the control group (44% and 52%, respectively; ch2 = 0.641; P = 0.424; OR = 0.85; 95% CI 0.330-. 1,594). At the level of distribution of heterozygous Gln / Glu genotypes, the results of both groups differed relatively weakly (40% and 44%, respectively; ch2 = 0.164; P = 0.686; OR = 0.848; 95% CI 0.383-1.879). At the homozygote Glu/Glu genotype distribution level, it was observed to be significantly higher in our baseline group than in the control group (16% and 4%, respectively; ch2 = 4; P = 0.046; OR = 4,571; 95% CI 0.919– 22.731).  From the calculated statistics, it can be seen that the comparative statistical difference between them is somewhat trending (see table).

Table 1.

Differences between allele and genotype distribution rate of ADRB2 gene rs1042714 polymorphism in baseline and control group samples

Thus, when comparing the prevalence of the allele and genotype of the rs1042714 polymorphism of the ADRB2 gene with patients from the main group and samples of practically healthy donors in the control group, it can be observed that the Glu allele and the Glu/Glu genotype in our control group predominate to a greater extent than in the control group. Group. In our literature review, the prevalence of the Glu isoform in the American population was found to be 24.6% among whites, 17.7% among blacks, and 9% among Chinese.

Thus, the Glu allele of the rs1042714 polymorphism of the ADRB2 gene (OR =1.54; 95% CI 1.008–3.432) and the Glu/Glu genotype (OR = 4.5; 95% CI 0.919–22.731) are important risks in the pathogenesis of MS in the Uzbek female. nation was a factor. In the homozygous Gln/Gln genotype, on the contrary, we can see that it has a protective protective role against the development of pathology.

Thus, the Glu allele of the rs1042714 polymorphism of the ADRB2 gene (OR = 1.54; 95% CI 1.008–3.432) and the Glu/Glu genotype (OR = 4.5; 95% CI 0.919–22.731) are important risks in the pathogenesis of MS in the Uzbek female. nation was a factor. In the homozygous Gln/Gln genotype, on the contrary, we can see that it has a protective protective role against the development of pathology.

As described above, we examined the main group of patients by dividing them into smaller groups. By studying the calculation of the prevalence of alleles and genotypes of ADRB2 rs1042714 gene polymorphisms in small groups, it is possible to increase the degree of dependence of OR and other statistical indicators on groups. This increases our ability to determine which process (protein, fat, or carbohydrate metabolism) is relatively impaired in the pathogenesis of MS, and to localize this gene determinant as the underlying cause. Therefore, in the later stages of our study, we tried to compare the samples of the control group with small groups.

Comparative analysis of the distribution frequency of alleles and genotypes of the rs1042714 polymorphism of the ADRB2 gene in obese patients with small-groupa MS with samples from the control group is presented in (table. 2.)

Table 2.

Comparative analysis of the prevalence of alleles and genotypes of the rs1042714 polymorphism of the ADRB2 gene in samples of patients with MS and obese patients in the main group (group A) and the control group

As can be seen from (table. 2), the Gln allele in the small-A and control groups was 61 and 76%, respectively, and the Glu allele was 39 and 24% (ch2 = 4.034; P = 0.045; OR = 2.05).; 95% CI 1012–4150). When divided into small groups, a relatively high shift (from 1.86 to 2.05) was observed in obese patients with the Glu allele and OR levels of MS. The prevalence of the Gln/Gln genotype in patients of the A-group subgroup was significantly lower than in the control group (32 and 52%, respectively; ch2 = 2.8; P = 0.09; OR = 0.437; 95% CI). 0.166-1.151). It was found that the prevalence of heterozygous Gln/Glu genotypes was not statistically significant in the samples of the control group (44%) and in the small group of patients A (46%) (ch2 = 0.043; P = 0.8; OR = 1.1; 95%). CI 0.436-2.793). The homozygous Glu/Glu genotype is small - we see that in patients of our group A it is 5.5 times higher than in the control group (22% and 4.0%; ch2 = 5.9; P = 0.015; OR = 6 .5, 95% CI 1.22). - 35.05).

The results of our observations show that homozygous Glu/Glu genotypes play an important role in the syntropic development of MS and obesity in our population (OR = 6.5; 95% CI 1.22-35.05), the influence of the heterozygous Gln/Glu genotype turned out to be  insignificant (OR = 1.1; 95% CI 0.436–2.793). On the contrary, we can see that the homozygous Gln/Gln genotype plays a relative protective role in the etiological syntropy of MS and obesity (P = 0.09; OR = 0.437; 95% CI 0.166–1.151).

At the next stage, a comparative analysis of the distribution of alleles and genotypes of the rs1042714 polymorphism of the ADRB2 gene in the pathogenesis of comorbid pathology of MS and CT in group B with samples from the control group is presented. The Gln allele in the small-B and control groups was 66% and 76%, respectively, and the Glu allele was 34% and 24%, respectively (ch2 = 1576; P = 0.21; OR = 0.61; 95% CI 0.282– 1.324.).

During the analysis, it was found that the prevalence of the Gln/Gln genotype in patients in the small - B group was higher than in the control group; 59% and 52% in our control group (ch2 = 1.5; P = 0.2; OR = 1.33; 95% CI 0.483–3.679). It was found that the frequency of occurrence of heterozygous Gln/Glu genotypes is higher in the samples of the control group (44%) than in the small group of patients in group B (32%) (ch2 = 0.94; P = 0.33; OR = 0).59; 95% CI 0.206–1.709). The homozygous Glu/Glu genotype is small - it can be seen that in our group B, the control is significantly higher than in the group, i.e. it was 9% and 4%, respectively (ch2 = 0.755; P = 0.38; OR = 2.4).; 95% CI 0.316-18.24) (see table 3).

Table 3.

Comparative analysis of the prevalence of alleles and genotypes of the rs1042714 polymorphism of the ADRB2 gene in patients with diabetes mellitus (subgroup B) and a sample of the control group among patients of the main group

Based on the above results, the Glu allele is less common in MS and DM syndromes than in healthy donors (OR = 0.7), but the homozygous genotype of the Glu allele is significantly higher (OR = 2.4). Thus, although the association of the Glu allele with the development of this disease is small, a high risk of developing the homozygous genotype of the Glu allele with a high risk of developing MS and QD syndrome has been identified, the significance of its significance has not been established (ch2 = 0.755); p = 0.38).

Conclusion

The study studied the Gln27Glu polymorphism of the ADRB2 gene. The main and control groups were selected. Initially, a comparative analysis of the distribution of allelic variants of the rs1042714 locus of the ADRB2 gene in the samples of the main and control groups showed that the Gln allele is 63% and 76%, respectively, and the Glu allele is 37% and 24%, respectively. (ch2 = 3.986; P = 0.046; OR = 1.86; 95% CI 1.008–3.432). It was noted that the prevalence of the Glu allele in our main group of patients was higher than in the samples of the control group and was statistically significant. These data indicate that the Gln27Glu genotypic variant of the ADRB2 gene plays an important role in the development of the metabolic syndrome and that the Gln27Glu rs 1042714 polymorphism is more common in obesity than in diabetes.

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