Polymorphisms of the Costimulatory Genes CTLA-4, CD28, PD-1, and ICOS and Outcome of Kidney Transplants in Iranian Patients

Objectives: Costimulatory molecules are important factors determining the outcome of transplant. The aim of the present study was to investigate the effect of CTLA-4, CD28, PD-1, and ICOS gene polymorphisms on the outcome of kidney transplant. Materials and Methods: A total of 172 kidney transplant recipients were included in this study. There were 45 recipients (26%) who experienced acute rejection. The CTLA-4, PD-1, ICOS, and CD28 gene polymorphisms were evaluated by polymerase chain reaction and restriction fragment length polymorphism methods. Results: There were no differences between kidney transplant recipients with or without acute rejection in the distribution of genotypes and alleles of studied costimulatory molecules. Significant associations were observed between the AA genotype and the A allele of CTLA-4 1661 (P =.04, P =.05) and also CT and TT genotypes of PD-1.9 in the male compared with female subgroup of patients, with low frequency in the acute rejection group (P =.03; P =.04). Significant associations were observed between the AA genotype and the A allele of CTLA-4 -1661 (P =.02; P =.01) and also GA genotype of PD-1.3 (P =.03) in the male subgroup compared with female subgroup with low frequency of acute rejection. A significant association was observed between TC genotype of CD28 in the female compared with male subgroup of patients with high frequency of acute rejection (P =.05). Conclusions: The above results suggest that genetic polymorphisms of costimulatory molecules function as sex-dependent risk factors for development of acute rejection. Further studies are needed in different populations.