Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to acute allograft rejection

Background. Cytotoxic T-lymphocyte antigen 4 (CTLA4) has been shown to play a critical role in the down-regulation of the immune response. We retrospe ctively examined the association between acute rejection and two polymorphi sms in the CTLA4 gene, the dinucleotide (AT). repeat polymorphism. in exon 3 and the single nucleotide polymorphism A/G at position 49 in exon 1, in a cohort of liver and kidney transplant recipients. Methods and Results. A total of 207 liver and 167 renal transplant recipien ts were analyzed. In the case of the (AT)(n) repeat polymorphism. we found an increased incidence of acute rejection in association with allele 3 and 4 in both liver and kidney (P=0.002 and 0.05, respectively). In addition, i n liver transplant recipients, allele 7 was associated with acute rejection independent of ethnicity (P <0.05). Allele 1 was less frequently observed in African American as compared with Caucasian liver and kidney transplant recipients, with a frequency of 33.8% and 69%, respectively (P <0.0001). Th ose patients with allele 1 had a tendency toward a lower rate of rejection at 42% versus 57.8% (P=0.058), suggesting a potential protective effect of allele 1. Analysis of the A/G single nucleotide polymorphism demonstrated n o association between either allele and the incidence of acute rejection in the patients studied. Conclusion. These initial observations provide the necessary basis to furth er investigate the risk stratification of transplant recipients based on sp ecific CTLA4 gene polymorphisms.