IL-10 polymorphisms +434T/C, +504G/T, and -2849C/T may predispose to tubulointersititial nephritis and uveitis in pediatric population.

<h4>Background</h4>Tubulointerstitial nephritis (TIN) and uveitis syndrome (TINU) are likely to be autoimmune diseases. Based on previous studies, adults with isolated idiopathic uveitis have polymorphisms in interleukin 10 (IL-10) and tumor necrosis factor α (TNF-α) genes. We aimed to evaluate the presence of IL-10 and TNF-α polymorphisms in a nationwide cohort of pediatric TIN/TINU patients.<h4>Methods</h4>Single nucleotide polymorphisms in IL-10 (+434T/C, +504G/T, -1082G/A, -2849C/T) and in TNFα (-308G/A, -238G/A, -857C/T) genes were genotyped in 30 well-defined pediatric patients with idiopathic TIN/TINU syndrome. Control group frequencies for these SNPs were obtained from 393 independent Finnish subjects.<h4>Results</h4>The homozygous minor allele in IL-10 +434T (rs2222202) and IL-10+504G (rs3024490) was found in all patients with TIN or TINU syndrome while the frequency of these minor alleles in the control population was 44% and 23%, respectively (p <0.001). In IL-10 SNP -2849 (rs6703630) a significant difference was found with genotype TT in all patients (p = 0.004) and in subgroups with TINU syndrome (p = 0.017) and TINU syndrome with chronic uveitis (p = 0.01) compared to reference population. There were no statistical differences in any of the studied TNF-α genotypes between TIN/TINU patients and control population.<h4>Conclusions</h4>A significant difference in the frequency of IL-10+434T and +504G alleles was found between TIN/TINU patients and control population. Genotype -2849TT was more frequently present in patients with TINU syndrome than in the reference subjects. Genetic variation in the inflammatory mediators may predispose to autoimmune nephritis and uveitis.

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   Genotype Imputation with Thousands of Genomes · 2011

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