Donor/Recipient Matching for the -174G/C SNP Polymorphism in the IL-6 Gene Promoter Influences the Outcome of Stem Cell Transplantation.

Background: Polymorphisms in regulatory sequences of cytokine genes are known to influence their expression and, therefore, the intensity of the immune response. Some of such polymorphisms have been associated with the outcome of stem cell transplantation (SCT), which supports the hypothesis of a genetic predisposition towards certain complications post-transplants.

Objective: To evaluate the association between donor (D) and recipient (R) genotype in the IL-6 gene -174G/C SNP polymorphism with the development of complete or mixed chimerism (MC) and, consequently, with complications such as graft rejection, graft versus host disease (GVHD) and survival after SCT.

Patients and methods: The study included 16 SCT (9 ablative, 3 T cell depleted, 4 reduced intensity conditioning). The IL-6 -174G/C SNP genotypes were determined by PCR on genomic DNA from Rs and Ds, using allele-specific oligonucleotides (ASO-PCR) as primers (forward: 5′-ccctagttgtgtcttgcc-3′ or 5-′ccctagttgtgtcttgcg-3′; reverse: 5′-gagcttctctttcgttcc-3′). Logistic regression was applied to identify associations between the polymorphism, the development of MC and of the mentioned complications. The reduced number of SCT analyzed, precluded the use of Pearson’s and/or Fisher’s p values or further statistics.

Results: The frequency of the different genotypes was 44.4% CC, 33.3% GC and 22.2% GG for Rs, and 33.3% CC, 44.4% GC and 22.2% GG for Ds. 88.9% D/R pairs were matched for the polymorphism and 11,1% mismatched. None of the patients transplanted from matched donors showed MC at any time post-SCT while all mismatched patients developed MC (Table 1). MC in the D/R mismatched group was associated with a greater rate of graft rejection and with a reduced incidence of acute GVHD (aGVHD) when compared with the D/R matched group (Table 1). No association was observed in this sample between the polymorphism analyzed and the development of chronic GVHD (cGVHD). Although graft rejection was early diagnosed and successfully treated with immunosuppression withdrawal and donor leukocyte infusion, the D/R matched group showed higher mortality rate that the mismatched group (Table 1).

Conclusions: The present study suggests an association between D/R matching for the IL-6 gene -174G/C SNP polymorphism and the development of MC and, consequently, of different complications after SCT. The analysis of a larger number of patients will eventually allow to confirm these observations as well as to establish this type of studies as a means for an improved management of transplanted patients.