A pilot study of single nucleotide polymorphisms in the interleukin-6 receptor and their effects on pre- and postransplant serum mediator level and outcome after allogeneic stem cell transplantation

Summary

Background: Interleukin 6 (IL-6) is an important regulator of immunity and inflammation in many diseases. Single nucleotide polymorphisms (SNPs) in the IL-6 gene influence outcome after allogeneic stem cell transplantation (ASCT), but the possible importance of SNPs in the IL-6 receptor has not been examined. We therefore investigated whether SNPs in the IL-6R gene influenced biochemical characteristics and clinical outcomes after ASCT.

Patients and methods: We investigated the IL-6 promoter variant rs1800975 and the IL-6R SNPs rs4453032, rs2228145, rs4129267, rs4845374, rs4329505, rs4845617, rs12083537, rs4845618, rs6698040 and rs4379670 in a 101 population-based cohort of allotransplant recipients and their family donors.

Results: Patients being homozygous for the major alleles of the IL-6R SNPs rs2228145 and rs4845618 showed high pre-transplant CRP serum levels together with decreased sIL-6R levels; the decreased IL-6R levels persisted 6 months post-transplant. In contrast, patients being homozygous for the minor allele of the IL6-R SNP rs4379670 showed decreased pretransplant CRP levels. Furthermore, the IL-6R rs4845618 donor genotype showed an association with severe acute graft versus host disease (GVHD), whereas the donor genotype of the IL-6 SNP rs1800795 was associated with decreased survival 100 days post-transplant. Finally, the recipient genotype of the IL-6R SNP rs4329505 showed a strong association with 2-years non-relapse mortality and this effect was highly significant also in multivariate analysis.

Conclusion: IL-6 and IL-6R SNPs influence the clinical outcome after allogeneic stem cell transplantation. This article is protected by copyright. All rights reserved.