Department of Pediatric and Adolescent, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China.
Department of Clinical Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China.
Curr Med Sci. 2023 Jun;43(3):585-591. doi: 10.1007/s11596-023-2728-3. Epub 2023 Apr 28.
Idiopathic nephrotic syndrome (INS) is the most common glomerular disease in children. Toll-like receptors (TLRs) have been reported to be associated with response to steroid treatment in children with INS. Nevertheless, the correlation between TLR genes and the progression of INS has not yet been clarified. The present study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) in TLR2, TLR4, and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.
A total of 183 pediatric inpatients with INS were included and given standard steroid therapy. Based on their clinical response to steroids, the patients were classified into three groups: steroid-sensitive nephrotic syndrome (SSNS), steroid-dependent nephrotic syndrome (SDNS), and steroid-resistant nephrotic syndrome (SRNS). A total of 100 healthy children were employed as controls. The blood genome DNA was extracted from each participant. Six SNPs (rs11536889, rs1927914, rs7869402, rs11536891, rs352140, and rs3804099) in TLR2, TLR4, and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.
Among the 183 patients with INS, 89 (48.6%) had SSNS, 73 (39.9%) had SDNS, and 21 (11.5%) had SRNS. No significant difference was found in the genotype distribution between healthy children and patients with INS. However, the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS. Compared with patients with the C allele and CC genotype, patients with the T allele and CT genotype had an increased risk of SRNS.
TLR4 rs7869402 affected the steroid response in Chinese children with INS. It might be a predictor for the early detection of SRNS in this population.
特发性肾病综合征（INS）是儿童中最常见的肾小球疾病。有报道称， Toll 样受体（TLR）与儿童 INS 对类固醇治疗的反应有关。然而，TLR 基因与 INS 进展之间的相关性尚未阐明。本研究旨在探讨 TLR2、TLR4 和 TLR9 单核苷酸多态性（SNP）与中国 INS 儿童易感性及对类固醇治疗反应的临床表型之间的关系。
共纳入 183 例 INS 住院患儿，给予标准类固醇治疗。根据对类固醇的临床反应，将患儿分为三组：类固醇敏感型肾病综合征（SSNS）、类固醇依赖型肾病综合征（SDNS）和类固醇抵抗型肾病综合征（SRNS）。共招募 100 名健康儿童作为对照。从每位参与者中提取血液基因组 DNA。选择 TLR2、TLR4 和 TLR9 中的 6 个 SNP（rs11536889、rs1927914、rs7869402、rs11536891、rs352140 和 rs3804099），通过下一代测序的多重聚合酶链反应检测 TLR 基因多态性。
在 183 例 INS 患儿中，89 例（48.6%）为 SSNS，73 例（39.9%）为 SDNS，21 例（11.5%）为 SRNS。健康儿童与 INS 患儿之间的基因型分布无显著差异。然而，TLR4 rs7869402 的基因型和等位基因频率在 SRNS 与 SSNS 之间存在显著差异。与 C 等位基因和 CC 基因型的患者相比，携带 T 等位基因和 CT 基因型的患者发生 SRNS 的风险增加。
TLR4 rs7869402 影响中国 INS 儿童对类固醇的反应。它可能是该人群中 SRNS 早期检测的预测因子。
