Association of the A/G polymorphism at position 49 in exon 1 of CTLA-4 with the susceptibility to unexplained recurrent spontaneous abortion in the Chinese population

PROBLEM: To investigate whether the A/G polymorphism at position 49 in exon 1 of cytotoxic T lymphocyte antigen-4 (CTLA-4) gene, which delivers a negative signal to T-cell activation, confers the susceptibility to unexplained recurrent spontaneous abortion in the Chinese population. METHOD OF STUDY: A total of 168 patients with unexplained recurrent spontaneous abortion (RSA), who were treated in the Renji Hospital affiliated to the Shanghai Second Medical University, were matched against 117 women with normal pregnancy history. Case-control study to compare the frequency of G/A alleles, AA/AG/GG genotypes and A + (AA + AG) /G+ (GG + AG) phenotypes of CTLA-4 between RSA patients and controls were performed. After amplification of CTLA-4 exon-1 region by polymerase chain reaction (PCR), restriction fragment-length polymorphism (RFLP) was used to detect the polymorphism at position 49 in exon-1 of CTLA-4 gene. Statistical significance was tested by SPSS software. RESULTS: There were dissimilar distributions of G/A alleles, AA/AG/GG genotypes and A+/G+ phenotypes of CTLA-4 between RSA patients and controls. The frequencies of G allele (P = 0.032) and GG genotype (P = 0.011) in RSA patients were significantly higher than those in controls, while the frequencies of AG genotype (P = 0.039) and A + (AA + AG) phenotype in RSA patients were decreased significantly (P = 0.011). CONCLUSIONS: Our findings suggest that A/G polymorphism in exon-1 of CTLA-4 is associated with the immunopathogenesis of RSA, and it confers susceptibility to RSA in Chinese population.