Heterozygosity in CTLA-4 gene and severe preeclampsia

One of the major complications of pregnancy, preeclampsia makes pregnancy termination inevitable in most cases. Similarities exist between the mechanisms that maintain normal pregnancy, allograft transplants, and, it is postulated, peripheral self-tolerance. In addition, the critical role of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) molecule in maintaining self-tolerance has been established. Therefore, the frequency of CTLA-4 A49G polymorphism was investigated in severe preeclampsia.

Genomic DNA extracted from mononuclear cells of the peripheral blood of 36 pregnant women with severe preeclampsia and 151 healthy women was analyzed. A49G polymorphism in position 49 of exon-1 of the CTLA-4 gene was studied by the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) method.

The frequency of the GG genotype was 2 (5.6%) in patients and 19 (12.6%) in controls, while the frequency of the AA genotype was 4 (11.1%) and 60 (39.7%). Interestingly, the frequency of the AG genotype was significantly higher in preeclamptic than in healthy women from the general population (83.3% vs. 47.7%; P=0.0005).

These data suggest that heterozygosity in the CTLA-4 A49G allele might be a predisposing factor for severe preeclampsia. Whether the observed association results from linkage imbalance with other loci on chromosome 2 or other polymorphisms of the CTLA-4 gene or even from a preferential transfer and/or expression of one allele from a heterozygous mother to the fetus will be the subject of future investigations.