P-212: Association between Polymorphisms of CTLA-4 Gene and Unexplained Recurrent Spontaneous Abortion in An Iranian Population

Background: Unexplained recurrent spontaneous abortion (URSA) has been suggested being associated with the failure of fetal-maternal immunologic tolerance in which the regulatory T lymphocytes (Tregs) play a crucial role. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is expressed transiently on activated T cells and constitutively on Tregs. CTLA-4 interacts with the B7 cell surface molecule on antigen-presenting cells and inhibits T-cell activation and proliferation. Recent Studies have reported that single-nucleotide polymorphisms (SNPs) in the CTLA-4 gene could contribute to susceptibility to some autoimmune disorders. However, the association between polymorphisms CTLA-4 of and URSA has not been defined well enough. This study evaluated the association between CTLA-4 gene SNPs and URSA in an Iranian population. Materials and Methods: In a case-control study, 195 patients with histories of at least three consecutive miscarriages with unexplained etiology before 20th week of gestation and 102 healthy women with at least two normal pregnancies were included as case and control groups, respectively. We genotyped two SNPs in the CTLA4 gene (a C/T transition at position -318 and A/G transition at position +49), using polymerase chain reaction- -restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The results showed that - 318C/T polymorphism (p<0.001) in CTLA4 gene promoter region differed significantly between URSA patients and controls, while no association was found between +49A/G in exon 1 polymorphism and URSA. Conclusion: Results from this study suggest that -318 C/T polymorphism of CTLA-4 gene promoter be associated with immunopathogenesis URSA, and individuals carrying this allele may be more susceptible to URSA.