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白细胞介素-17A 基因多态性与埃及儿童和青少年系统性红斑狼疮易感性的关联:一项多中心研究。

Association of interleukin-17A gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multi-centre study.

机构信息

Department of Paediatrics, Faculty of Medicine, Zagazig University, Egypt.

Department of Paediatrics, Faculty of Medicine, Ain-Shams University, Egypt.

出版信息

Lupus. 2020 Jun;29(7):767-775. doi: 10.1177/0961203320922305. Epub 2020 May 7.

DOI:10.1177/0961203320922305
PMID:32380889
Abstract

BACKGROUND

Recently, the interleukin-17A () gene has emerged as a potential candidate gene for autoimmune disorders, including systemic lupus erythematosus (SLE).

OBJECTIVES

This study aimed to investigate whether IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T could be susceptibility markers for juvenile-onset SLE (JSLE) and lupus nephritis (LN) in Egyptian children and adolescents.

METHODS

In this multi-centre study, we genotyped 320 patients diagnosed with JSLE and 320 matched control children for three IL-17A polymorphisms at rs2275913 G/A, rs8193036 C/T and rs3748067 C/T using TaqMan probe-based real-time polymerase chain reaction. Meanwhile, IL-17A serum levels were assessed using ELISA.

RESULTS

The IL-17 rs2275913 A/A genotype and A allele were more represented in JSLE patients compared to the control group (21% vs. 7%, odds ratio (OR) = 3.8, 95% confidence interval (CI) 1.78-5.5,  = 0.001, Bonf = 0.003 for the A/A genotype; 37% vs. 29%, OR = 1.4, 95% CI 1.11-1.8,  = 0.003, Bonf = 0.009 for the A allele. No significant difference was found for IL-17 rs8193036 and rs3748067 single nucleotide polymorphisms (SNPs) in genotype distribution or allele frequencies (>0.05). Patients carrying the IL-17 rs2275913 A/A genotype and A allele were more likely to develop LN (OR = 5.64, 95% CI 2.39-13.77, Bonf = 0.001 for the A/A genotype; OR = 2.73, 95% CI 1.84-4.07, Bonf = 0.02 for the A allele).

CONCLUSION

The IL-17 rs2275913 A allele and A/A genotype were associated with high IL-17 serum levels and may contribute to susceptibility to JSLE and the development of LN in Egyptian children and adolescents. However, no significant association was evident between the studied IL-17A SNPs and other clinical phenotypes, disease activity scores or laboratory profile of JSLE.

摘要

背景

最近,白细胞介素-17A()基因已成为包括系统性红斑狼疮(SLE)在内的自身免疫性疾病的潜在候选基因。

目的

本研究旨在探讨白细胞介素-17A 基因 rs2275913 处的 G/A、rs8193036 处的 C/T 和 rs3748067 处的 C/T 多态性是否可作为埃及儿童和青少年幼年特发性关节炎(JSLE)和狼疮性肾炎(LN)的易感标志物。

方法

在这项多中心研究中,我们使用 TaqMan 探针实时聚合酶链反应,对 320 名确诊为 JSLE 的患者和 320 名匹配的对照儿童进行 IL-17A 基因 rs2275913 G/A、rs8193036 C/T 和 rs3748067 C/T 三种多态性的基因分型。同时,采用 ELISA 法检测血清 IL-17A 水平。

结果

与对照组相比,JSLE 患者中 IL-17 基因 rs2275913 的 A/A 基因型和 A 等位基因更为常见(21% vs. 7%,比值比(OR)=3.8,95%置信区间(CI)1.78-5.5,=0.001,Bonf=0.003;37% vs. 29%,OR=1.4,95%CI 1.11-1.8,=0.003,Bonf=0.009)。IL-17 基因 rs8193036 和 rs3748067 单核苷酸多态性(SNP)在基因型分布或等位基因频率上无显著差异(>0.05)。携带 IL-17 基因 rs2275913 的 A/A 基因型和 A 等位基因的患者更易发生 LN(OR=5.64,95%CI 2.39-13.77,Bonf=0.001;OR=2.73,95%CI 1.84-4.07,Bonf=0.02)。

结论

IL-17 基因 rs2275913 的 A 等位基因和 A/A 基因型与高血清 IL-17 水平相关,可能导致儿童和青少年易患 JSLE 和发生 LN。然而,在所研究的 IL-17A SNP 与其他临床表型、疾病活动评分或 JSLE 的实验室特征之间未发现显著关联。

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