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血清白细胞介素-17A浓度和白细胞介素17受体A单核苷酸多态性与自身免疫性1型糖尿病的风险相关。

Serum IL-17A concentration and a IL17RA single nucleotide polymorphism contribute to the risk of autoimmune type 1 diabetes.

作者信息

Li Junxian, Xu Lei, Zhao Weijing, Pan Jiemin, Lu Junxi, Lu Huijuan, Yan Jinhua, Weng Jianping, Liu Fang

机构信息

Department of Endocrinology & Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Diabetes Metab Res Rev. 2022 Sep;38(6):e3547. doi: 10.1002/dmrr.3547. Epub 2022 May 25.

Abstract

AIMS

Interleukin (IL)-17 is associated with autoimmunity. This study aimed to affirm the role of IL-17A, IL-17F and single nucleotide polymorphisms (SNPs) in genes related to them and their receptors in autoimmune type 1 diabetes (T1D) for Chinese population.

METHODS

In this study, 130 patients with autoimmune T1D and 140 non-T1D controls were included for analysis. Clinical and biochemical data were collected, and serum levels of IL-17A, IL-17F, IL-6, and high-sensitivity C reactive protein were measured using ELISA. The SNPs rs2275913, rs8193036, rs3819025, rs763780, rs879577, rs4819554, and rs708567 were genotyped using the SNaPshot assay.

RESULTS

IL-17A levels were higher in patients with autoimmune T1D than in controls (median [IQR] 28.83[37.38] vs. 16.68[8.10], p < 0.001) and high IL-17A was a risk factor for autoimmune T1D (odds ratio (OR), 1.013; 95% CI, 1.003-1.023; p = 0.013) after adjusting for confounding factors. Linear regression analysis revealed that log IL-17A levels were independently associated with fasting C-peptide, IL-6, body mass index, and IL-17F. However, no independent association was found between IL-17F and autoimmune T1D. The GG genotype of SNP rs4819554 in the interleukin 17 receptor A (IL17RA) gene was associated with a decreased risk of autoimmune T1D (OR, 0.458; 95% CI, 0.246-0.852; p = 0.014) after adjusting for other confounders. The IL17RA rs4819554 GG genotype was negatively correlated with serum glutamic acid decarboxylase antibody appearance (p < 0.05).

CONCLUSIONS

Increased serum IL-17A, but not IL-17F, is a risk factor for autoimmune T1D. The GG genotype of IL17RA rs4819554 might decrease the risk for autoimmune T1D.

摘要

目的

白细胞介素(IL)-17与自身免疫性疾病相关。本研究旨在明确IL-17A、IL-17F及其相关基因和受体的单核苷酸多态性(SNP)在中国人群自身免疫性1型糖尿病(T1D)中的作用。

方法

本研究纳入130例自身免疫性T1D患者和140例非T1D对照进行分析。收集临床和生化数据,采用酶联免疫吸附测定法(ELISA)检测血清IL-17A、IL-17F、IL-6和高敏C反应蛋白水平。使用SNaPshot分析法对SNP rs2275913、rs8193036、rs3819025、rs763780、rs879577、rs4819554和rs708567进行基因分型。

结果

自身免疫性T1D患者血清IL-17A水平高于对照组(中位数[四分位间距]28.83[37.38] vs. 16.68[8.10],p < 0.001),校正混杂因素后,高IL-17A水平是自身免疫性T1D的危险因素(比值比(OR),1.013;95%可信区间,1.003 - 1.023;p = 0.013)。线性回归分析显示,log IL-17A水平与空腹C肽、IL-6、体重指数和IL-17F独立相关。然而,未发现IL-17F与自身免疫性T1D之间存在独立关联。白细胞介素17受体A(IL17RA)基因SNP rs4819554的GG基因型与自身免疫性T1D风险降低相关(OR,0.458;95%可信区间,0.246 - 0.852;p = 0.014),校正其他混杂因素后。IL17RA rs4819554 GG基因型与血清谷氨酸脱羧酶抗体出现呈负相关(p < 0.05)。

结论

血清IL-17A水平升高而非IL-17F水平升高是自身免疫性T1D的危险因素。IL17RA rs4819554的GG基因型可能降低自身免疫性T1D的风险。

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