Association between single nucleotide polymorphism of immunoregulatory genes and preterm premature rupture of membranes in preterm labour

Authors

  • K. S. Liubomyrska Zaporizhzhia State Medical University, Ukraine,
  • O. M. Kamyshnyi Zaporizhzhia State Medical University, Ukraine,
  • Yu. Ya. Krut Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1237.2018.2.141400

Keywords:

preterm labour, preterm premature rupture of membranes, single nucleotide polymorphism

Abstract

Aim. Investigation of the association between SNP genes of IL4 (rs2243250), IL10 (rs1800896 and rs1800872) and RLN2 (rs4742076 and rs3758239) and preterm premature rupture of membranes in 26–34 weeks of gestation in Zaporizhzhia population.

Materials and methods. We have investigated markers of cytokines genes in 50 women with PPROM in 26–34 weeks of gestation period and 50 pregnant women with physiological pregnancy and term labour without complications. The genotyping using TaqMan tests was done on amplifier CFX96™ Real-Time PCR Detection Systems (Bio-Rad Laboratories, Inc., USA. The combined effect of the studied locus of the analyzed genes on the appearance of PPROM, PTL in the population was initiated using the Multifactory Dimensionality Reduction (MDR) method (software MDR ver. 3.0.2).

Results. The distribution of the rs2243250 gene polymorphism alleles of the IL4 gene of the main study group – TT homozygotes were determined in 4 % cases, CT heterozygotes were found in 22 %, CC homozygotes – in 74 % cases. We have got statistically significant differences of rs4742076 polymorphisms (TT, CT, and CC) of the RLN2 gene in the study groups. We also detected statistically significant differences in all the alleles of rs3758239 polymorphism (AA, GG and AG) of the gene RLN2 – χ2 = 23.86, OR(AA) = 12.57; 95 % CI: 3.68–42.98; OR(GG)= 0.08; 95 % CI: 0.02–0.27; and OR(AG)= 0.11; 95 % CI: 0.03–0.42, respectively, P < 0.05, indicating the reliability of the received prognostic markers. The nature of interlocal interaction between the genes is at the level of “independent effects” of influence (IL4-IL10 rs1800896 = -23.08 %, IL10 rs1800896 – IL10 rs1800872 = -19.94 %, IL10 rs1800872-IL-4 = -19.34 %). The percentage of entropy of the investigated polymorphism of each gene for the case-control status was 14.15 % for the IL4 gene, 23.08 % for the IL10 rs1800896 gene and 9.34 % for the IL10 rs1800872 gene.

Conclusions. Combination of IL4 rs2243250, IL10 rs1800896 and rs1800872 supports the role for functional polymorphisms in immunoregulatory genes in the development of PPROM and PTL. Reliable clinical association of rs4742076 and rs3758239 gene RLN2 was established with the PPROM in 26–34 weeks’ gestation in Zaporizhzhia population.

 

References

Stonek, F., Metzenbauer, M., Hafner, E., Phillip, K., & Tempfer, C. (2008). Interleukin-10-1082 G/A promoter polymorphism and pregnancy complications: results of prospective cohort study in 1616 pregnant women. Acta Obstet Gynecol Scand. – Acta Obstet Gynecol Scand., 87, 430–43. doi: 10.1080/00016340801995657.

Heinzmann, A., Mailaparambil, B., Mingirulli, N., & Krueger, M. (2009). Association of Interleukin 13/4 and toll-like receptor 10 with preterm births. Neonatology, 96(3), 175–81. doi: 10.1159/000210091.

Ramos, B. R., Mendes, N. D., Tanikawa, A. A., Amador, M. A., dos Santos, N. P., dos Santos, S. E., et al. (2016). Ancestry informative markers and selected single nucleotide polymorphisms in immunoregulatory genes on preterm labor and preterm premature rupture of membranes: a case control study. BMC Pregnancy Childbirth, 16, 30. doi: 10.1186/s12884-016-0823-1.

Zare-Bidaki, M., Sadrinia, S., Erfani, S., Afkar, E., & Ghanbarzade, N. (2017). Antimicrobial properties of amniotic and chorionic membranes: a comparative study of two human fetal sacs. J Reprod Infertil, 18(2), 218–224.

Tchirikov, M., Schlabritz-Loutsevitch, N., Maher, J., Buchmann, J., Naberezhnev, Y., Winarno, A. S., & Seliger, G. (2018). Mid-trimester preterm premature rupture of membranes (PPROM): etiology, diagnosis, classification, international recommendations of treatment options and outcome. J. Perinat. Med., 46(5), 465–488. doi: 10.1515/jpm-2017-0027.

Bukowski, R., Sadovsky, Y., Goodarzi, H., Zhang, H., Biggio, J. R., Varner, M., et al. (2017). Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface. Peer J., 5, e3685. doi: 10.7717/peerj.3685.

Musilova, I., Kutová, R., Pliskova, L., Stepan, M., Menon, R., Jacobsson, B., & Kacerovsky, M. (2015). Intraamniotic inflammation in women with preterm prelabour rupture of membranes. Plos One., 10(7), e0133929 doi: 10.1371/journal.pone.0133929.

Sneikh, A. I., Ahmad, E., Jamal, M. S., Rehan, M., Assidi, M., Tayubi, I. A., et al. (2016). Spontaneous preterm birth and single nucleotide gene polymorphisms: a recent update. BMC Genomics, 17(Suppl 9), 759. doi: 10.1186/s12864-016-3089-0.

Rocha, F. G., Slavin, T. P., Li, D., Tiirikainen, M. I., & Bryant-Greenwood, G. D. (2013). Genetic associations of relaxin: preterm birth and premature rupture of fetal membranes. Am J Obstet Gynecol., 209(3), 258.e1–8. doi: 10.1016/j.ajog.2013.05.020.

Salema, H., Yatchenko, E., Anosova, M., Rosenfeld, T., Altarescub, G., Grisaru-Granovsky, S., & Birk, R. (2018). Maternal and neonatal irisin precursor gene FNDC5 polymorphism is associated with preterm birth. Gene., 649, 58–62. doi: 10.1016/j.gene.2018.01.097.

National Center for Biotechnology information, dbSNP database. Retrieved from http://www.ncbi.nim.nih.gov/SNP/.

Wang, Y., H. Luo, G. Che, Y. Li, J., Gao, J., Yang, Q., et al. (2018). Placental protein 14 as a potential biomarker for diagnosis of preterm premature rupture of membranes. Mol Med Rep., 18(1), 113–122. doi: 10.3892/mmr.2018.8967.

Vogel, I., Hollegaard, M. V., Hougaard, D. M., Thorsen, P., & Grove, J. (2009). Polymorphism in the promoter region of relaxin-2 and preterm birth: involvement of relaxin in the etiology of preterm birth. In Vivo, 23(6), 1005–9.

Downloads

How to Cite

1.
Liubomyrska KS, Kamyshnyi OM, Krut YY. Association between single nucleotide polymorphism of immunoregulatory genes and preterm premature rupture of membranes in preterm labour. Pathologia [Internet]. 2018Sep.12 [cited 2024Dec.24];(2). Available from: http://pat.zsmu.edu.ua/article/view/141400

Issue

Section

Original research