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CTLA-4 gene polymorphisms and risk of idiopathic recurrent pregnancy loss in a Tunisian population

Background

An aberrant regulation of immunological, metabolic, vascular and endocrine processes leads to obstetric complications, including recurrent pregnancy loss (RPL) [1]. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a negative regulator of T cell activation [2] expressed in placental fibroblasts and may modulate peripheral self-tolerance of the allogenic fetus [3, 4]. It is a stimulatory molecule involved in T-cell activation at the maternal–fetal interface in women with unexplained pregnancy loss [5, 6]. In this study, we investigate the possible associations of Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms with idiopathic recurrent pregnancy loss (RPL).

Materials and methods

We investigated the association of the CTLA-4 gene single nucleotide polymorphisms (SNPs) -318 C/T (rs5742909), +49A/G (rs231775), and CT60 A/G (rs3087243), by TaqMan assays in analysis in 470 Tunisian women comprising 235 RPL cases and 235 multi-parous controls. The association of CTLA-4 alleles, genotypes, and haplotypes with RPL was evaluated by Fisher's exact test and regression analysis.

Results

The CTLA-4 variants rs5742909, rs231775, and rs3087243, were in Hardy Weinberg equilibrium, and low linkage disequilibrium was noted between the three studied SNPs. The frequency of rs231775 G allele (P=0.04), but not rs3087243 G allele (P=0.61) or rs5742909 T allele (P=1), was higher in RPL cases than in control women. Significant differences in the distribution of rs231775 (P<0.02), but not rs5742909 (P=0.21) or rs3087243 (P=0.49) genotypes were seen between cases and controls, and only rs231775 showed a significant association with RPL, with increments of 1.74 in disease risk seen for heterozygous carriers. Only rs231775 (+49/A/G), previously shown associated with the immuno-pathogenesis of RPL, and it confers susceptibility to RPL in Chinese population [5] and North Indian Women [7], was significantly associated with RPL. Among the six three-locus CTLA-4 haplotypes constructed (rs5742909/rs231775/rs3087243), increased frequency of CGA (P=0.0046), and CAG (P=0.036) haplotypes were seen in RPL cases, thus conferring disease susceptibility nature to these haplotypes.

Conclusions

The rs231775 AG genotype and CGA and CAG haplotypes may contribute to RPL development in a Tunisian Population.

References

  1. Baek KH: Aberrant gene expression associated with recurrent pregnancy loss. Mol Hum Reprod. 2004, 10 (5): 291-7.

    Article  CAS  PubMed  Google Scholar 

  2. Bashyam H: CTLA-4: From conflict to clinic. J Exp Med. 2007, 204 (6): 1243-

    Article  PubMed Central  PubMed  Google Scholar 

  3. Anjos SM, Polychronakos C: Functional evaluation of the autoimmunity-associated CTLA-4 gene: the effect of the (AT) repeat in the 3'untranslated region (UTR). J Autoimmun. 2006, 27 (2): 105-9.

    Article  CAS  PubMed  Google Scholar 

  4. Kaufman KA, Bowen JA, Tsai AF, Bluestone JA, Hunt JS, Ober C: The CTLA-4 gene is expressed in placental fibroblasts.MHR: Basic science of reprod. Medicine. 1998, 5 (1): 84-87.

    Google Scholar 

  5. Wang X, Lin Q, Ma Z, Hong Y, Zhao A, Di W, Lu P: Association of the A/G polymorphism at position 49 in exon 1 of CTLA-4 with the susceptibility tounexplained recurrent spontaneous abortion in the Chinese population. Am J Reprod Immunol. 2005, 53 (2): 100-5.

    Article  CAS  PubMed  Google Scholar 

  6. Wang X, Ma Z, Hong Y, Lu P, Line Q: Expression of CD28 and cytotoxic T lymphocyte antigen 4 at the maternal–fetal interface in women with unexplained pregnancy loss. International Journal of Gynecology & Obstetrics. 2006, 93 (2): 123-129.

    Article  CAS  Google Scholar 

  7. Gupta , et al: Association of CTLA-4 and TNF-α polymorphism with recurrent miscarriage among North Indian women. Cytokine. 2012, 60 (2): 456-62.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Safia Messaoudi.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Messaoudi, S., Houas, I., Yaseen, K. et al. CTLA-4 gene polymorphisms and risk of idiopathic recurrent pregnancy loss in a Tunisian population. BMC Genomics 15 (Suppl 2), P11 (2014). https://0-doi-org.brum.beds.ac.uk/10.1186/1471-2164-15-S2-P11

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  • DOI: https://0-doi-org.brum.beds.ac.uk/10.1186/1471-2164-15-S2-P11

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