PEDEGO Research Unit and Medical Research Center (MRC), University of Oulu and Oulu University Hospital, Oulu, Finland.
Clinical Laboratory, Finnish Red Cross Blood Service, Helsinki, Finland.
PLoS One. 2019 Feb 19;14(2):e0211915. doi: 10.1371/journal.pone.0211915. eCollection 2019.
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.
肾小管间质性肾炎（TIN）和葡萄膜炎综合征（TINU）可能是自身免疫性疾病。基于以往的研究，成人孤立性特发性葡萄膜炎存在白细胞介素 10（IL-10）和肿瘤坏死因子α（TNF-α）基因的多态性。我们旨在评估全国性儿科 TIN/TINU 患者队列中 IL-10 和 TNF-α 多态性的存在。
对 30 例明确诊断的特发性 TIN/TINU 综合征患儿的 IL-10（+434T/C、+504G/T、-1082G/A、-2849C/T）和 TNFα（-308G/A、-238G/A、-857C/T）基因的单核苷酸多态性进行了基因分型。这些 SNP 的对照组频率是从 393 名独立的芬兰受试者中获得的。
TIN 或 TINU 综合征患者中均发现 IL-10+434T（rs2222202）和 IL-10+504G（rs3024490）纯合子的次要等位基因，而在对照组中这些次要等位基因的频率分别为 44%和 23%（p<0.001）。在 IL-10 SNP-2849（rs6703630）中，所有患者（p=0.004）和 TINU 综合征亚组（p=0.017）和 TINU 综合征伴慢性葡萄膜炎亚组（p=0.01）的 TT 基因型与参考人群相比存在显著差异。在 TIN/TINU 患者和对照组中，TNF-α 基因型之间没有统计学差异。
TIN/TINU 患者和对照组之间 IL-10+434T 和+504G 等位基因的频率存在显著差异。TINU 综合征患者中-2849TT 基因型比参考人群更常见。炎症介质的遗传变异可能导致自身免疫性肾炎和葡萄膜炎。
