Genotype complexes of some cytokines in the constitutional predisposition of Russian women of Caucasian origin to the development of uterine leiomyoma

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Abstract

Objective: This study aimed to compare the distribution of single nucleotide polymorphisms (SNP) in the regulatory regions of proinflammatory and anti-inflammatory cytokine genes between patients with uterine leiomyoma (UL) and healthy women in the Caucasian population of Western Siberia. Additionally, this study assessed the prognostic significance of genetic differences.

Materials and methods: An observational genetic case-control study involving 180 women with UL (aged 23-61 years) and 98 healthy women of the same age was conducted using real-time PCR. Ten SNPs of pro-inflammatory cytokine genes were studied: tumor necrosis factor (TNF) TNF-863C/A, TNF-308G/A, TNF-238G/A, interleukins (IL) IL1B-31T/C, IL6-174C/G, IL8-251T/A, IL17-197A/G, and anti-inflammatory cytokines IL4-590C/T, IL10-592A/C, and IL-10-1082A/G. Standard methods of genetic and bioinformatics analysis were used.

Results: A comparative analysis of the distribution frequency of the 10 SNPs of cytokine genes identified 587 statistically significant complex genotypes associated positively or negatively with the development of UL after Bonferroni correction. The strongest positive associations were observed for combinations of genotypes TNF-308G/G and IL17-197A/A (OR=7.03, p=0.0162), IL10-1082A/G and IL17-197A/A (OR=10.78, p=0.0423), TNF-308G/G, IL6-174G/C, IL10-592C/C and IL10-1082A/G (OR=12.81, p=0.0414), with prognostic values for UL development ranging from 82 to 100%. Conversely, complex genotypes indicating resistance to UL development (p<0.01) were identified in comparison to the control group, with a prognostic value for a specific woman ranging from 87 to 100%.

Conclusion: The data obtained from this study can be used to establish a set of personalized prognostic indicators for a woman's genetic predisposition or resistance to UL development, even before the disease manifests.

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About the authors

Vladimir I. Konenkov

Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: vikonenkov@gmail.com
ORCID iD: 0000-0001-7385-6270

Dr. Med. Sci., Professor, Academician of the RAS, Head of the Clinical Immunogenetics Laboratory

Russian Federation, Novosibirsk

Elena G. Koroleva

Novosibirsk Novosibirsk State Medical University, Ministry of Health of Russia

Email: korlex71@mail.ru
ORCID iD: 0000-0002-8522-4382

obstetrician-gynecologist, Junior Researcher at the Laboratory of Cellular Biology and Fundamental Basis of Reproduction of Central Scientific Laboratory

Russian Federation, Novosibirsk

Viktor F. Prokofiev

Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Author for correspondence.
Email: vf_prok@mail.ru
ORCID iD: 0000-0001-7290-1631

PhD, Leading Researcher at Clinical Immunogenetics Laboratory

Russian Federation, Novosibirsk

Alla V. Shevchenko

Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: vf_prok@mail.ru
ORCID iD: 0000-0001-5898-950X

Dr. Biol. Sci., Leading Researcher at Clinical Immunogenetics Laboratory

Russian Federation, Novosibirsk

Yulia S. Timofeeva

Novosibirsk Novosibirsk State Medical University, Ministry of Health of Russia

Email: dr.j.timofeeva@yandex.ru
ORCID iD: 0000-0002-5379-9296

PhD, Teaching Assistant at the Obstetrics and Gynecology Department

Russian Federation, Novosibirsk

Svetlana V. Aidagulova

Novosibirsk Novosibirsk State Medical University, Ministry of Health of Russia

Email: asvetvlad@yandex.ru
ORCID iD: 0000-0001-7124-1969

Dr. Biol. Sci., Professor, Head of the Laboratory of Cellular Biology and Fundamental Basis of Reproduction of Central Scientific Laboratory

Russian Federation, Novosibirsk

Igor O. Marinkin

Novosibirsk Novosibirsk State Medical University, Ministry of Health of Russia

Email: rector@ngmu.ru
ORCID iD: 0000-0002-9409-4823

Dr. Med. Sci., Professor, Head of the Obstetrics and Gynecology Department, Rector

Russian Federation, Novosibirsk

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