CTLA-4 and IL-6 gene polymorphisms: Risk factors for recurrent pregnancy loss.

The purpose of the present study was to evaluate the possible association between CTLA-4 +49A/G and IL-6 -634C/G polymorphisms, and the risk of recurrent pregnancy loss (RPL). 240 women (120 healthy controls and 120 with RPL) were enrolled in this case-control study. Genotyping was performed using a PCR-RFLP technique. In the case of polymorphic CTLA-4 +49A/G, the wild type allele G was associated with a decreased risk of RPL (OR: 0.42, 95%CI: 0.25-0.69, p=0.001). As to IL-6 -634C/G polymorphism, a highly significant difference was observed, and those women who carry at least one mutant G allele presented a probability of developing RPL about 5 times greater than controls (OR: 5.1, 95%CI: 1.04-25.3, p=0.04). The results indicate that polymorphisms of CTLA-4 and IL-6 genes may influence the risk of developing RPL among Iranian women, suggesting that more research on the immunogenetics of pregnancy should be conducted to confirm our results, and to declare the exact roles of studied molecules in RPL pathogenesis.

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

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.

The IL-6 -634C/G polymorphism: a candidate genetic marker for the prediction of idiopathic recurrent pregnancy loss.

BACKGROUND: Recurrent pregnancy loss (RPL) is defined as two or more miscarriages before the 20(th) week of gestation and its etiology is unknown in 50% of the cases. Interleukin 6 is an immune mediator, plays a regulatory role in embryo implantation and placental development. OBJECTIVE: The purpose was to assess the association between IL-6 -634C/G polymorphism and, susceptibility to idiopathic RPL for the first time in Iran. MATERIALS AND METHODS: In total 121 women with RPL and 121 healthy women as control group were enrolled in this case-control study. This study was performed from August 2013 to October 2014 in the Molecular Genetics Laboratory of Arsanjan University. Candidate polymorphism was evaluated by PCR-RFLP method on extracted genomic DNA. Data was analyzed using the statistical SPSS package. RESULTS: Our results showed an increased risk of RPL in patients with GG + GC genotype (OR=5.1, 95%CI: 1.04-25.3, p=0.04) in comparison to CC genotype. The frequency of mutant allele G in patients and controls was 0.75 and 0.66 respectively. The mutant allele G predisposes women to miscarriage 1.5 times greater than controls (OR=1.5, 95%CI: 1.03-2.27, p=0.036). The mean number of live births in RPL women (1.3±2.3) was significantly lower compared to control women (4.8±2.3). CONCLUSION: This study indicated that the promoter polymorphism (-634C/G) of the IL-6 gene has likely influence on individual susceptibility to RPL.