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


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2019
Historique:
received: 06 10 2018
accepted: 22 01 2019
entrez: 20 2 2019
pubmed: 20 2 2019
medline: 5 11 2019
Statut: epublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.

Identifiants

pubmed: 30779760
doi: 10.1371/journal.pone.0211915
pii: PONE-D-18-29043
pmc: PMC6380573
doi:

Substances chimiques

IL10 protein, human 0
Interleukin-10 130068-27-8

Types de publication

Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0211915

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Sari Rytkönen (S)

PEDEGO Research Unit and Medical Research Center (MRC), University of Oulu and Oulu University Hospital, Oulu, Finland.

Jarmo Ritari (J)

Clinical Laboratory, Finnish Red Cross Blood Service, Helsinki, Finland.

Juha Peräsaari (J)

Clinical Laboratory, Finnish Red Cross Blood Service, Helsinki, Finland.

Ville Saarela (V)

Ville Saarela, Department of Ophthalmology, Oulu University Hospital, Finland.

Matti Nuutinen (M)

PEDEGO Research Unit and Medical Research Center (MRC), University of Oulu and Oulu University Hospital, Oulu, Finland.

Timo Jahnukainen (T)

Timo Jahnukainen, Department of Pediatric Nephrology and Transplantation, New Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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Classifications MeSH