Identification and association of RAC1 gene polymorphisms with mRNA and protein expression levels of Rac1 in solid organ (kidney, liver, heart) transplant recipients

摘要

The activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) is critical in the renal, hepatic and cardiac diseases that lead to the requirement for transplantation, however, no investigations have been performed in Chinese populations to determine the association between RAC1 genotypes and the activation of Rac1. In the present study, 304 solid organ transplant recipients (SOTRs), consisting of 164 renal transplantations, 85 hepatic transplantations and 55 cardiac transplantations, and 332 Chinese healthy control subjects were recruited to investigate whether differences existed in the mRNA and protein expression levels of Rac1 in the different groups. Furthermore, the present study identified and investigated associations of the RAC1 (rs702482, rs10951982, rs702483 and rs6954996) genotypes with the mRNA expression levels of RAC1, and the protein expression levels of total Rac1 and active Rac1-guanosine triphosphatase (GTP). It was identified that the healthy population had significantly kidney, liver and heart transplantation populations (P<0.001 for all comparisons). Significant associations (P<0.05) were observed between the RAC1 genotypes and the expression levels of mRNA, Rac1 and Rac1-GTP. However, the changes in the mRNA expression levels of RAC1 with genotypes were different from those of the proteins. The results of the present study represent the first, to the best of our knowledge, to report that Rac1 and Rac1-GTP proteins can be downregulated in SOTRs, and that RAC1 genetic polymorphisms can potentially affect the mRNA expression of RAC1, and the protein expression of Rac1 and Rac1-GTP. These results provide a foundation for further functional investigations to determine the biological and molecular functions of the RAC1 gene in SOTRs.