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. 2016 Jul-Sep;17(3):151-6.

Association of the +49 A/G Polymorphism of CTLA4 Gene with Idiopathic Recurrent Spontaneous Abortion in Women in Southwest of Iran

Zarnegar Rasti  1 , Mahboobeh Nasiri  1
Affiliations

Association of the +49 A/G Polymorphism of CTLA4 Gene with Idiopathic Recurrent Spontaneous Abortion in Women in Southwest of Iran

Zarnegar Rasti et al. J Reprod Infertil. 2016 Jul-Sep.

Abstract

Background: Survival of the semi-allograft fetus during pregnancy opens a new area for the immunological based causes of recurrent spontaneous abortion (RSA). Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is a negative regulator of the T-cell activation, which may modulate peripheral self-tolerance of the allogeneic fetus. The present study aimed to investigate the +49 A/G CTLA4 genetic polymorphism and predisposition to RSA.

Methods: The total participants were 120 women with at least two miscarriages and 120 healthy post-menopausal women as the control group. The +49 A/G polymorphism was genotyped using PCR-RFLP method. Required demographic information was collected through filling out a questionnaire. The obtained data were fed into SPSS software version 16.

Results: The results showed a significant association between the minor alleles (G) with the decreased risk of the RSA. The frequency of the G allele in controls and patients was 25% and 12%, respectively. A GG genotype in the co-dominance model (OR: 0.25, 95%CI: 0.09-0.66) and in the dominant model for allele G (GG+AG vs. AA) (OR: 0.84, 95%CI: 0.8-0.87) showed significant association with RSA by imposing the protective role. The frequency of miscarriage is significantly (p=0.04) higher among the relatives of RSA women (33.3%) in comparison with the women in the control group (21.7%).

Conclusion: It can be concluded that +49G allele may act as a dominant allele and reduce the risk of RSA. Family history of miscarriage increased the risk of RSA among women.

Keywords: CTLA4; PCR-RFLP; Polymorphism; Recurrent spontaneous abortion.

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Figures

Figure 1.
Figure 1.
PCR-based restriction analysis of the +49 A/G polymorphism was shown on 2% agarose electrophoresis. The polymorphic region was amplified by PCR resulting in a 289 bp fragment (AA wild type homozygote) in line 3 after size marker. Digestible fragments, 159 and 130 bp, represent the GG mutant homozygote (line 2). The presence of three bands 289, 159 and 130 which belong to heterozygote individuals (line 1, 4 and 5). M: mar
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