Clinical significance of gene polymorphisms in the development of metabolic syndrome in the young population


DOI: https://dx.doi.org/10.18565/therapy.2021.9.28-36

Korneeva E.V., Voevoda M.I., Semaev S.E., Maksimov V.N.

1) Surgut State University; 2) Federal Research Center for Fundamental and Translational Medicine, Novosibirsk; 3) Research Institute of Therapy and Preventive Medicine – a branch of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk
Abstract. The widespread prevalence of high-calorie nutrition in countries with a high living standard in combination with a decrease in muscle energy expenditure leads to the formation of insulin resistance mechanism in the genetic memory and metabolic syndrome (MS) development.
The aim of the research is to study the influence of gene polymorphisms at metabolic disorders develooment among young inhabitants of the North.
Material and methods. A prospective cohort study of 883 young people living in conditions equivalent to the Far North conditions for a long time (average duration of residence – 27,9±0,005 years) for the period 2015–2020 was performed. 749 patients had MS and 134 were without MS manifestations. Within the framework of the performed molecular genetic study, the following gene polymorphisms were studied: rs1378942 of the CSK gene, rs1801133 (C677T) of the MTHFR gene, ITGA2B gene, rs7903146 of the TCF7L2 gene, rs1799752 of the ACE gene. Genomic DNA was isolated from venous blood by phenol-chloroform extraction methodic. Gene polymorphism was tested by means of polymerase chain reaction with polymorphism of restriction fragments’ lengths.
Results. While assessing anthropometric data and laboratory test results, patients with MS revealed hyperglycemia in 31,8%, hyperinsulinemia – in 13,8%, HDL hypocholesterolemia - in 19.4%, hypertriglyceridemia – in 78,1%, arterial hypertension – in 14,1% of cases. In the total sample of examined individuals, among the studied polymorphic loci, the loci of the ACE and CSK genes were more common. When analyzing the distribution of genotype pairs among the examined MS patients in the general cohort, the most common were combinations of polymorphism of the ITGA2B gene and the polymorphic locus rs1378942 of the CSK gene (18,0%). At the same time, these type of correlations were find more often among the indigenous (18,9%) and non-indigenous rural (18,6%) residents of the North. In case of combination of MS components, were most often detected polymorphisms of genes including heterozygous genotypes ID of the ACE, ITGA2B gene, homozygous CC genotypes of TCF7L2 and MTHFR genes, and heterozygous GT genotype of the CSK gene.
Conclusion. Clinical manifestations of MS in examined non-indigenous and indigenous young inhabitants of the North are caused by complex intergenic interactions of the studied single nucleotide polymorphisms of five genes: ACE, TCF7L2, ITGA2B, CSK, MTHFR. Combinations of mutant gene polymorphisms were found more common – heterozygous genotypes ID of the ACE, ITGA2B gene, homozygous CC genotypes of TCF7L2 and MTHFR genes, heterozygous GT genotype of CSK gene. Among them, the CSK gene plays a predominant role in MS development. Early identification of genetic predictors of metabolic disorders is of great clinical importance for timely prevention of cardiovascular diseases and diabetes mellitus development.
Keywords: abdominal obesity, hypertriglyceridemia, gene polymorphism, metabolic syndrome, arterial hypertension, hyperglycemia
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About the Autors

Elena V. Korneeva, PhD, associate professor of the Department of internal medicine, Surgut State University. Address: 628408, Surgut, 1 Lenina Avenue. E-mail: evkorneeva39@rambler.ru. ORCID: 0000-0002-0143-982x
Mikhail I. Voevoda, MD, professor, academician of RAS, director of Federal Research Center for Fundamental and Translational Medicine. Address: 630117, Novosibirsk, 2 Timakova Str. E-mail: mvoevoda@ya.ru. ORCID: 0000-0003-4716-876X
Sergey E. Semaev, junior researcher of the Laboratory of molecular genetic research of therapeutic diseases, Research Institute of Therapy and Preventive Medicine – a branch of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences. Address: 630089, Novosibirsk, 175/1 Borisa Bogatkova Str. E-mail: niitpm.office@gmail.com. ORCID: 0000-0003-3999-8501
Vladimir N. Maksimov, MD, professor, head of the Laboratory of molecular genetic studies of therapeutic diseases, Research Institute of Therapy and Preventive Medicine – a branch of Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences. Address: 630089, Novosibirsk, 175/1 Borisa Bogatkova Str. E-mail: medik11@mail.ru. ORCID: 0000-0002-7165-4496


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