Features of gene-gene and gene-factor interactions in men from couples with infertility and reproductive losses

24 жовтня 2018
1067
Резюме

Gene-gene and gene-factor interactions of genes polymorphic variants of hemostasis: ITGA2a (C807T), ITGB3b (T1565C), FGB (C148T, G–455A), PAI-1 (–675 5G/4G), FII (G20210A), FV (G1691A), of folate metabolism: MTHFR (C677T, A1298C), MTRR (A66G), MTR1 (A2756G), RFC1 (G80A) and follicle-stimulating hormone receptor gene FSHr (Ala307Thr, Ser680Asn) has been analyzed in 206 men from couples with unexplained infertility and early reproductive losses. A comparison of obtained results conducted using the methods of single — and multivariate statistical analysis. The association of ITGB3b, ITGA2a, RFC1, FSHr genes and their combinations with the risk of infertility in men has been proven. Five prognostic risk models were significant: gene-gene interaction (PAI-1 + ITGB3b + ITGA2a, MTHFR + MTR1 + RFC1) and gene-factor interaction (ITGB3b + prothrombin time, MTHFR + MTR1 + RFC1 + smoking, FSHr + MTRR + hereditary burden). The founded dependencies indicated a variety of individual pathogenetic mechanisms in development of men infertility that requires the use of personalized treatment.

N.G. Gorovenko, Z.I. Rossokha, S.P. Kiryachenko, L.P. Sheiko, L.I. Brisevac

Key words: genetic polymorphism, reproductive disorders, men.

Published: 29.10.2018

References:

  • Gorovenko N.G., Kiryachenko S.P., Rossoha Z.I. (2011) Izuchenie assotsiatsii polimorfnyih variantov genov ACE (I/D), AT2R1 (A1166C), TNF-a (G308A), MTHFR (C677T) i ih kombinatsiy c riskom razvitiya perinatalnoy patologii i sokrascheniem srokov gestatsii. Biopolym. Cell, 27(3): 206–213.
  • Zhylkova E.S. (2017) Henetychni aspekty reproduktyvnoi funktsii u cholovikiv u skhidnii Ukraini. avtoref. … kand. biol. nauk. Kyiv, 25 s.
  • Zotova T.Yu., Myandina G.I. (2013) Vliyanie polimorfizma gena ITGB3 na chastotu razvitiya arterialnoy gipertenzii u bolnyih s ostryim koronarnyim sindromom. med., 8: 22–27.
  • Abarikwu S.O. (2013) Causes and risk factors for male-factor infertility in Nigeria: a review. Afr. J. Reprod. Health, 17(4): 150–166.
  • Agarwal A., Mulgund A., Hamada A., Chyatte M.R. (2015) A unique view on male infertility around the globe. Reprod. Biol. Endocrinol., 13: 37.
  • Bueno O., Molloy A.M., Fernandez-Ballart J.D. et al. (2016) Common Polymorphisms That Affect Folate Transport or Metabolism Modify the Effect of the MTHFR 677C>T Polymorphism on Folate Status. J. Nutr., 146(1): 1–8.
  • Devalia V., Hamilton M.S., Molloy A.M.; British Committee for Standards in Haematology (2014) Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br. J. Haematol., 166(4): 496–513.
  • Gelineau-van Waes J., Maddox J.R., Smith L.M. et al. (2008) Microarray analysis of E9.5 reduced folate carrier (RFC1; Slc19a1) knockout embryos reveals altered expression of genes in the cubilin-megalin multiligand endocytic receptor complex. BMC Genomics, 9: 156.
  • Hong H.H., Hu Y., Yu X.Q. et al. (2017) Associations of C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene with male infertility risk: A meta-analysis. Eur. J. Obstet. Gynecol. Reprod. Biol., 212: 101–109.
  • Jungwirth A., Diemer T., Dohle G.R. et al. (2015) Guidelines on Male Infertility (https://uroweb.org/wp-content/uploads/17-Male-Infertility_LR1.pdf).
  • Kliesch S. (2014) Diagnosis of Male Infertility: Diagnostic Work-up of the Infertile Man. Eur. Urol., 13: 73–82.
  • Kucharska-Newton A.M., Monda K.L., Campbell S. et al. (2011) Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: the Atherosclerosis Risk in Communities (ARIC) Study. Atherosclerosis, 216(1): 151–156.
  • Massart A., Lissens W., Tournaye H., Stouffs K. (2012) Genetic causes of spermatogenic failure. Asian J. Androl., 14(1): 40–48.
  • Pietrzik K., Bailey L., Shane B. (2010) Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin. Pharmacokinet., 49(8): 535–548.
  • Rossokha Z., Gorovenko N. (2017) Assessment of the individual folic acid doses requirement for patient with reproductive disorders. J. Perinat. Med., 45(2): 349.
  • Stanger O., Herrmann W., Pietrzik K. et al. (2003) DACH-LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin. Chem. Lab. Med., 41(11): 1392–1403.
  • Taneja S.S. (2014) Current management of male infertility. Urol. Clin. North Am., 41(1): xv.
  • Visentin M., Diop-Bove N., Zhao R., Goldman I.D. (2014) The intestinal absorption of folates. Ann. Rev. Physiol., 76: 251–274.
  • Wilcken B. (2017) Therapeutic targets in homocystinuria due to cystathionine β-synthase deficiency: new European guidelines. Exp. Opin. Orph. Drugs, 5: 1–3.
  • Wosnitzer M.S. (2014) Genetic evaluation of male infertility. Transl. Androl. Urol., 3(1): 17–26.
  • Zorrilla M., Yatsenko A.N. (2013) The Genetics of Infertility: Current Status of the Field. Curr. Genet. Med. Rep., 1(4) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3885174/).