DOI: https://doi.org/10.22263/2312-4156.2020.3.50
Kononenko I.S.
Genes polymorphisms of transforming growth factor β1 and matrix metalloproteinase 9 as molecular and genetic predictors of isthmic-cervical insufficiency development in female patients with undifferentiated connective tissue dysplasia
Vitebsk State Order of Peoples’ Friendship Medical University, Vitebsk, Republic of Belarus
Vestnik VGMU. 2020;19(3):50-58.
Abstract.
Undifferentiated connective tissue dysplasia is a widespread condition among reproductive age women (from 53% to 68.8%). This makes it actual to study the role of genetically determined pathological connective tissue metabolism in female patients with this hereditary syndrome in the development of isthmic-cervical insufficiency (CI).
Objectives. To assess the association between single nucleotide polymorphisms (SNPs) A-8202G (rs11697325) MMP9 of the gene, and also Arg25Pro (rs1800471) TGFβ1 gene and isthmic-cervical insufficiency in female patients with undifferentiated connective tissue dysplasia.
Material and methods. A «case-control» study has been carried out. Medical, obstetric histories and blood samples were obtained from 71 pregnant women at 22-24 weeks of singleton pregnancy with (n=36) and without (n=35) undifferentiated connective tissue dysplasia and CI. Samples were analyzed by using an allele-specific polymerase chain reaction assay for variants in two genes, the ММР9 and TGFβ1, encoding proteins, participating in connective tissue metabolism. Serum levels of ММР9 and TGFβ1 were determined by enzyme immunoassay (ELISA).
Results. Two genotypes were significantly associated with isthmic-cervical insufficiency compared with controls: homozygous carriers of the ММР9 -8202G allele (genotype G/G) (OR=4.00, 95% CI 1.23-12.98, p=0.02) and carriers of Arg/Pro genotype of the TGFβ1 (OR=3.75, 95% CI 1.88-7.47, p<0.0001). Carriers of these genotypes had significantly higher serum levels of encoded by them proteins.
Conclusions. GG genotype of the A-8202G polymorphism of ММР9 gene and ArgPro genotype of the Arg25Pro polymorphism of TGFβ1 gene are associated with a high risk of isthmic-cervical insufficiency development in female patients with undifferentiated connective tissue dysplasia.
Key words: gene polymorphism, isthmic-cervical insufficiency, undifferentiated connective tissue dysplasia, transforming growth factor β1 (TGFβ1), matrix metalloproteinase 9 (ММР9).
Financing: This research was carried out within the frames of intra-University scientific startup-grant for young scientists of «Vitebsk State order of Peoples’ Friendship medical University» in 2019.
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Information about authors:
Kononenko I.S. – lecturer of the Chair of Obstetrics and Gynecology, Vitebsk State Order of Peoples’ Friendship Medical University,
ORCID: https://orcid.org/0000-0002-4915-8269.
Correspondence address: Republic of Belarus, 210009, Vitebsk, 27 Frunze ave., Vitebsk State Order of Peoples’ Friendship Medical University, Chair of Obstetrics and Gynecology. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Irina S. Kononenko.
