Cytokine Gene Polymorphism Profiles in Kidney Transplant Patients - Association of +1188A/C RS3212227 SNP in the IL12B Gene Prevents Delayed Graft Function

Vladimir Perovic; Milos Markovic; Milica Kravljaca; Emina Milosevic; Milica Djoric; Vera Pravica; Radomir Naumovic

doi:10.1016/j.arcmed.2018.04.015

Cytokine Gene Polymorphism Profiles in Kidney Transplant Patients - Association of +1188A/C RS3212227 SNP in the IL12B Gene Prevents Delayed Graft Function

Arch Med Res. 2018 Feb;49(2):101-108. doi: 10.1016/j.arcmed.2018.04.015. Epub 2018 May 10.

Authors

Vladimir Perovic¹, Milos Markovic², Milica Kravljaca³, Emina Milosevic², Milica Djoric², Vera Pravica², Radomir Naumovic⁴

Affiliations

¹ Department of Immunology, Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: vladimir.perovic@med.bg.ac.rs.
² Department of Immunology, Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
³ Clinic of Nephrology, Clinical Center of Serbia, Belgrade, Serbia.
⁴ Clinic of Nephrology, Clinical Center of Serbia, Belgrade, Serbia; Department of Internal Medicine, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

PMID: 29754746
DOI: 10.1016/j.arcmed.2018.04.015

Abstract

Background and aims: Transplantation is the best treatment option for end stage kidney disease. The most common early complications in post-transplant period are acute rejection (AR) of the graft and delayed graft function (DGF). The underlying mechanisms in these events are heterogeneous and at least in part involve cytokine genes which regulate immune response to allograft. We have investigated whether functional single nucleotide polymorphisms (SNP) in the genes encoding IFN-γ (IFNG), TNF (TNFA), IL-10 (IL10) and p40 subunit of IL-12/IL-23 (IL12B) could predict risk of AR and DGF in kidney allograft recipients.

Methods: Our study involved 152 kidney transplant recipients on standard immunosuppressive regimen which included calcineurin inhibitors, mycophenolic acid derivatives and corticosteroids. Genotyping of IFNG, TNFA, IL10 and IL12B was performed using commercial TaqMan assays.

Results: We found association between the carriers of AA genotype of IL12B +1188A/C polymorphism (rs3212227) and a lower rate of DGF (p = 0.037, OR = 0.45, 95% CI = 0.21-0.96), implying protective role of A allele in the pathogenesis of DGF in kidney transplant recipients, whereas no such association was observed with AR. None of the analyzed SNPs in TNFA (-308G/A), IFNG (+874T/A), IL10 (-1082G/A, -819T/C, -592C/A) were associated with AR or DGF in our patients.

Conclusions: Our study shows a preliminary evidence that the AA genotype of rs3212227 SNP in the IL12B gene might be associated with a lower risk for DGF after kidney transplantation. In the future, additional well-designed large studies are required for the validation of our results.

Keywords: Acute rejection; Cytokine polymorphisms; Delayed graft function; IL12B; Kidney transplantation; rs3212227.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alleles
Delayed Graft Function / genetics*
Female
Genetic Association Studies
Genotyping Techniques
Graft Rejection / genetics*
Humans
Interferon-gamma / genetics
Interleukin-10 / genetics
Interleukin-12 Subunit p40 / genetics*
Kidney Failure, Chronic / genetics
Kidney Failure, Chronic / surgery*
Kidney Transplantation*
Male
Middle Aged
Polymorphism, Single Nucleotide / genetics
Tumor Necrosis Factor-alpha / genetics

Substances

IFNG protein, human
IL10 protein, human
IL12B protein, human
Interleukin-12 Subunit p40
TNF protein, human
Tumor Necrosis Factor-alpha
Interleukin-10
Interferon-gamma