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The role of FAS, FAS-L, BAX, and BCL-2 gene polymorphisms in determining susceptibility to unexplained recurrent pregnancy loss

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Idiopathic recurrent pregnancy loss (RPL) is a multifactorial reproductive disorder where an impaired control of apoptosis is likely involved. Triggering the cell death mechanism occurs in a spatiotemporal manner and is strongly related to a healthy pregnancy. Single nucleotide polymorphisms (SNPs) at the regulatory regions of genes are known to influence the expression patterns of apoptosis-related molecules.

Methods

A total of 296 unrelated female Brazilian patients were evaluated for clinical-demographic variables and genetic factors: 140 women who had experienced an unexplained RPL (with at least two consecutive abortions) and 156 healthy multiparous women. In all patients, six SNPs were evaluated in genes of apoptosis-related pathways: FAS (rs2234767, rs1800682), FAS-L (rs763110, rs5030772), BAX (rs4645878), and BCL-2 (rs2279115) by PCR followed by a restriction fragment length polymorphism (RFLP)-based analysis.

Results

The BAX-248GA genotype is independently associated with idiopathic RPL [adjusted OR = 0.30, 95% CI 0.13–0.70, P = 0.005] susceptibility. In the same multivariate model, the variables ethnicity, smoking, and alcohol consumption were statistically associated with RPL susceptibility (P < 0.05). No association with RPL susceptibility was reported for the remaining SNPs.

Conclusion

Our study is the first to evaluate the role of the main SNPs from both the extrinsic and intrinsic apoptosis pathways in RPL susceptibility. The association of BAX-248G/A with RPL susceptibility suggests that maternal predisposition for RPL has an essential contribution from genes involved in the delicate balance of endometrium cell turnover (cell death/proliferation). Therefore, apoptotic genes may represent promising targets for future studies on healthy pregnancies and the spectrum of pregnancy disorders.

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Funding

This study was supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (grant no. 14/2253-2 PqG) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (grant nos. 473115/2011-5 and 305839/2015-2).

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Authors and Affiliations

  1. Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul (UFRGS), Bento Gonçalves Avenue 9500, Campus do Vale, Porto Alegre, RS, CEP 91501970, Brazil

    Rafael Tomoya Michita, Francis Maria Báo Zambra, Lucas Rosa Fraga, Maria Teresa Sanseverino, Lavínia Schuler-Faccini, José Artur Bogo Chies & Priscila Vianna

  2. National Institute of Science and Technology in Population Medical Genetics (INAGEMP), Porto Alegre, RS, Brazil

    Maria Teresa Sanseverino & Lavínia Schuler-Faccini

  3. Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Maria Teresa Sanseverino & Lavínia Schuler-Faccini

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  1. Rafael Tomoya Michita
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  2. Francis Maria Báo Zambra
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  3. Lucas Rosa Fraga
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  4. Maria Teresa Sanseverino
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  6. José Artur Bogo Chies
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  7. Priscila Vianna
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Corresponding author

Correspondence to José Artur Bogo Chies.

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This study was approved by the Research Ethics Committee of the HCPA (HCPA-CEP-CPPG) under protocol number #11-242. We obtained written, informed consent according to the Declaration of Helsinki from all individual participants included in this study.

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Michita, R.T., Zambra, F.M.B., Fraga, L.R. et al. The role of FAS, FAS-L, BAX, and BCL-2 gene polymorphisms in determining susceptibility to unexplained recurrent pregnancy loss. J Assist Reprod Genet 36, 995–1002 (2019). https://doi.org/10.1007/s10815-019-01441-w

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