ESPN 50th Annual Meeting

ESPN 2017


 
IL-10 POLYMORPHISMS IN CHILDREN WITH TUBULOINTERSTITAL NEPHRITIS AND UVEITIS
SARI RYTKÖNEN 1 Jarmo Ritari 4 Juha Peräsaari 4 Ville Saarela 3 Matti Nuutinen 1 Timo Jahnukainen 2

1- PEDEGO RESEARCH UNIT AND MEDICAL RESEARCH CENTER (MRC) OULU, UNIVERSITY OF OULU AND OULU UNIVERSITY HOSPITAL, OULU, FINLAND
2- Department of Pediatric Nephrology and Transplantation, Children’s Hospital, Helsinki University Hospital and Helsinki University, Helsinki, Finland
3- Department of Ophthalmology, Oulu University Hospital, Oulu, Finland
4- Clinical Laboratory, Finnish Red Cross Blood Service, Helsinki, Finland
 
Introduction:

Tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) is a rare condition with various etiology. Both TIN and TINU syndrome have been shown to be enriched in patients with certain HLA type potentially reflecting underlying autoimmune mechanisms. It has also been previously shown that Interleukin 10 (IL-10) and tumor necrosis factor α (TNFα) polymorphisms are associated with idiopathic and non-infectious uveitis. IL10 is an important immunoregulatory cytokine inhibiting T cells, monocytes, and macrophages. TNFα is it´s counter regulator inducing inflammation. In this study we investigated IL10 and TNFα polymorphisms in TIN/TINU patients.

Material and methods:

Four IL-10 and three TNFα single nucleotide polymorphisms (SNP) (rs1800629, rs361525, rs1800896, rs1799724, rs2222202, rs3024490 and rs6703630) were genotyped in 30 pediatric patients with TIN/TINU syndrome. Control group frequencies for these SNPs were obtained from both Illumina Immunochip analysis of 587 Finnish siblings and from 1000 Genomes project Finnish population subset (n=99). Fisher’s exact test was performed for significance of association for SNP frequencies between patients and controls. Finally, all raw p-values were adjusted for multiple testing by the Benjamini-Hochberg method.

Results:

A significant increase in the frequency of IL-10 +434T (rs2222202) and IL-10+504G (rs3024490) alleles was found in all patients and in TIN/TINU subgroups separately when compared to the Finnish reference population (100% vs. 40% and 76% respectively, p= <0.05). There were no statistical differences in any of the studied TNFα genotypes between TIN/TINU patients and control population.

Conclusions:

A significant difference in the frequency of IL-10+434T and +504G alleles was found in our patient cohort. This genetic variation in the inflammatory mediators may predispose to inflammatory diseases.