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  • 53 -12 (50) 2022 — Yariev A.A., Boboev K.T., — STUDY OF THE ASSOCIATION OF THE POLYMORPHISM RSL799750 GENE MMP1 AND RS2276109 GENE MMP12 WITH THE DEVELOPMENT OF VARICOSIS OF THE LEG AND ITS TROMBOTHIC COMPLICATIONS

53 -12 (50) 2022 — Yariev A.A., Boboev K.T., — STUDY OF THE ASSOCIATION OF THE POLYMORPHISM RSL799750 GENE MMP1 AND RS2276109 GENE MMP12 WITH THE DEVELOPMENT OF VARICOSIS OF THE LEG AND ITS TROMBOTHIC COMPLICATIONS

STUDY OF THE ASSOCIATION OF THE POLYMORPHISM RSL799750 GENE MMP1 AND RS2276109 GENE MMP12 WITH THE DEVELOPMENT OF VARICOSIS OF THE LEG AND ITS TROMBOTHIC COMPLICATIONS

Yariev A.A., Syrdarya branch of the Republican Scientific Center of  Emergency Medicine (RRCEM) MoH RUz

Boboev K.T., Head of Laboratory of Medical Genetics, Republican Specialized Scientific-Practical Medical Center of Hematology (RSSPMCH) MoH RUz,

Tadjibaev Alisher Tyxta-Pylatovic Surgeon of Syrdarya branch of the Republican Scientific Center of Emergency Medicine (RRCEM) MoH RUz

Resume

Assessment of the contribution of the rsl799750 polymorphism of the MMP1 gene of the rs2276109 and locus of the MMP12 gene to the development of lower limb varicose veins (VVLE) and its thrombotic complications.

Material and methods. A total of 316 people were enrolled in the study, 161 patients with VVLE and venous thrombosis were included in the main group, and 155 conditionally healthy individuals were included in the control group. The frequency of detection of the rsl799750 polymorphism of the MMP1 gene and rs2276109 of the MMP12 was investigated in all subjects using the Real-time PCR method.

Results. Study of the distribution of the mutant homozygous 2G/2G rs1799750 genotype of the MMP1 gene revealed a marked tendency for its prevalence in the subgroup of patients with venous thrombosis, where its proportion was 30.0%, versus the control group, where it was detected in 18.7% of cases, respectively (χ2=3.5; p=0.06; RR=1.8; 95% CI: 0.97-3.5 OR=2.3; 95% CI: 0.95-5.4). A mutant homozygous G/G rs2276109 genotype in the MMP12 gene was detected in one patient with VBNA complicated by venous thrombosis: 2.0% versus 0.6%, respectively (χ2=0.6; p=0.4; RR=2.0; 95% CI: 0.5-8.1; OR=3.0, 95% CI: 0.2-48.2).

Conclusions: Carriage of 2G/2G genotypic variant of rs1799750 polymorphism of MMP1 gene is reliably associated not only with VVLE formation but also with the development of venous thrombosis.

The presence of unfavorable allelic variant of rs7123600 polymorphism of MMP-12 gene may not serve as an early marker of development of structural changes of vein wall and VVLE of lower limbs as well as development of thrombotic complications.

Keywords: rsl799750, MMP1 gene, rs2276109, MMP12 gene, VVLE, complications, venous thrombosis, thrombotic complications.

First page

305

Last page

315

For citation:Yariev A.A., Boboev K.T., Tadjibaev Alisher Tyxta-Pylatovic STUDY OF THE ASSOCIATION OF THE POLYMORPHISM RSL799750 GENE MMP1 AND RS2276109 GENE MMP12 WITH THE DEVELOPMENT OF VARICOSIS OF THE LEG AND ITS TROMBOTHIC COMPLICATIONS //New Day in Medicine 12(50)2022 305-315 https://clck.ru/339bpH

LIST OF REFERENCES:

  1. Bharath V., Kahn S.R., Lazo-Langner A. Genetic polymorphisms of vein wall remodeling in chronic venous disease: a narrative and systematic review //Blood, The Journal of the American Society of Hematology. – 2014. – Т. 124. – №. 8. – С. 1242-1250.
  2. Fukaya E., Flores A.M., Lindholm D., Gustafsson S., Zanetti D., Ingelsson E., Leeper N.J. Clinical and Genetic Determinants of Varicose Veins. //Circulation. 2018 Dec 18; 138(25): 2869-2880.
  3. Ghaffarzadeh A., Bagheri M., Khadem-Vatani K., Abdi Rad I. Association of MMP-1 (rs1799750)-1607 2G/2G and MMP-3 (rs3025058)-1612 6A/6A Genotypes With Coronary Artery Disease Risk Among Iranian Turks. //J. Cardiovasc Pharmacol. 2019;74(5):420-425.
  4. Gillespie D., Patel A., Fileta B., Chang A., Barnes S., Flagg A., Kidwell M., Villavicencio J., Rich N. Varicose veins possess greater quantities of MMP-1 than normal veins and demonstrate regional variation in MMP-1 and MMP-13. //J Surg Res. 2002;106(2):233-238.
  5. Gomez I., Benyahia C., Louedec L., Leséche G., Jacob M.P., Longrois D., Norel X. Decreased PGE content reduces MMP-1 activity and consequently increases collagen density in human varicose vein. //PLoS One. 2014;5;9(2):88021.
  6. Görmüş U., Kahraman O., Isbir S., Tekeli A., Isbir T. MMP2 gene polymorphisms and MMP2 mRNA levels in patients with superficial varices of lower extremities. //In Vivo. 2011;25(3):387-391 [19]
  7. Görmüs U., Timirci-Kahraman O., Ergen A., Kunt A., Isbir S., Dalan A., Isbir T. Expression levels of elastin and related genes in human varicose veins. //Folia Biol. 2014;60(2):68-73. [17]
  8. Hollingsworth S.J., Powell G.l., Barker S.G., Cooper D.G. Primary varicose veins: altered transcription of VEGF and its receptors (KDR, fl t-1, soluble fl t-1) with sapheno-femoral junction incompetence //Eur J Vasc Endovasc Surg. 2004. Vol. 27, no. 3. рр. 259-268.
  9. Slonková V. et al. Genetic predisposition for chronic venous insufficiency in several genes for matrix metalloproteinases (MMP-2, MMP-9, MMP-12) and their inhibitor TIMP-2 //Journal of the European Academy of Dermatology and Venereology. – 2017. – Т. 31. – №. 10. – С. 1746-1752.
  10. Jang-Young Kim. Polymorphisms of MMP-3, MMP-9, MMP-12, and TIMP-1 genes as a determinant of isolated coronary artery ectasia: дис. – Graduate School, Yonsei University, 2007. – С. 1-41.
  11. Joseph N., Mohamed Faizan Thouseef A.B., Devi U.M., Abna A., Juneja I. A multicenter review of epidemiology and management of varicose veins for national guidance. //Annals of medicine and surgery. 2016;8:21-27.
  12. Klupp F., Neumann L., Kahlert C. et al. Serum MMP7, MMP10 and MMP12 level as negative prognostic markers in colon cancer patients. //BMC Cancer 16, 494 (2016) 1-9.
  13. Kowalewski R., Sobolewski K., Wolanska M., Gacko M. Matrix metalloproteinases in the vein wall. //Int Angiol. 2004;23(2):164-169.
  14. Su L., Zhou W., Asomaning K., Lin X., Wain J.C., Lynch T.J., Liu G., Christiani D.C. Genotypes and haplotypes of matrix metalloproteinase 1, 3 and 12 genes and the risk of lung cance //Carcinogenesis. 2006. no. 27. рр. 1024–1029.
  15. Ye S., Eriksson P., Hamsten A., Kurkinen M., Humphries S.E., Henney A.M. Progression of coronary atherosclerosis is associated with a common genetic variant of the human stromelysin-1 promoter which results in reduced gene expression //J Biol Chem. 1996. no. 271. рр. 13055–13060.
  16. Shapiro S.D., Kobayashi8 D.K., Ley T.J. Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages //J Biol Chem. 1993. no. 268. рр. 23824-23829. 
  17. Seryapina Y.U.V. et al. The genetic predictors of varicose veins of small pelvis: a pilot study //Flebologiya. – 2018. – Т. 12. – №. 1. – С. 25-29.
  18. Nüllen H., Noppeney T. Diagnosis and treatment of varicose veins. Part 1: definition, epidemiology, etiology, classification, clinical aspects, diagnostic and indications. //Der Chirurg; Zeitschrift fur AlleGebiete der Operativen Medizen. 2010; 81(11):1035-1044.
  19. Xu Y., Bei Y., Li Y., Chu H. Phenotypic and functional transformation in smooth muscle cells derived from varicose veins. //J Vasc Surgery Venous Lymphat Disord. 2017; 5(5):723-733.
  20. Lim C., Davies A. Pathogenesis of primary varicose veins. //Br J Surg. 2009; 96(11):1231-1142. https://doi.org/10.1002/bjs.6798 [8]

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