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基于基因和实验室数据的中国人群川崎病静脉注射免疫球蛋白抵抗预测模型。

Predictive model based on gene and laboratory data for intravenous immunoglobulin resistance in Kawasaki disease in a Chinese population.

机构信息

Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China.

Department of Cardiology, Children's Hospital Capital Institute of Pediatrics, No. 2 Ya-Bao Road, Chao Yang District, Beijing, 100020, China.

出版信息

Pediatr Rheumatol Online J. 2021 Jun 26;19(1):95. doi: 10.1186/s12969-021-00582-6.

Abstract

BACKGROUND

Here, we investigated the predictive efficiency of a newly developed model based on single nucleotide polymorphisms (SNPs) and laboratory data for intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD) in a Chinese population.

METHODS

Data relating to children with KD were acquired from a single center between December 2015 and August 2019 and used to screen target SNPs. We then developed a predictive model of IVIG resistance using previous laboratory parameters. We then validated our model using data acquired from children with KD attending a second center between January and December 2019.

RESULTS

Analysis showed that rs10056474 GG, rs746994GG, rs76863441GT, rs16944 (CT/TT), and rs1143627 (CT/CC), increased the risk of IVIG-resistance in KD patients (odds ratio, OR > 1). The new predictive model, which combined SNP data with a previous model derived from laboratory data, significantly increased the area under the receiver-operator-characteristic curves (AUC) (0.832, 95% CI: 0.776-0.878 vs 0.793, 95%CI:0.734-0.844, P < 0.05) in the development dataset, and (0.820, 95% CI: 0.730-0.889 vs 0.749, 95% CI: 0.652-0.830, P < 0.05) in the validation dataset. The sensitivity and specificity of the new assay were 65.33% (95% CI: 53.5-76.0%) and 86.67% (95% CI: 80.2-91.7%) in the development dataset and 77.14% (95% CI: 59.9-89.6%) and 86.15% (95% CI: 75.3-93.5%) in the validation dataset.

CONCLUSION

Analysis showed that rs10056474 and rs746994 in the SMAD5 gene, rs76863441 in the PLA2G7 gene, and rs16944 or rs1143627 in the interleukin (IL)-1B gene, were associated with IVIG resistant KD in a Chinese population. The new model combined SNPs with laboratory data and improved the predictve efficiency of IVIG-resistant KD.

摘要

背景

在这里,我们研究了一种基于单核苷酸多态性(SNP)和实验室数据的新模型,用于预测中国人群川崎病(KD)对静脉注射免疫球蛋白(IVIG)的耐药性。

方法

我们从 2015 年 12 月至 2019 年 8 月期间的一家单一中心获得与 KD 患儿相关的数据,用于筛选目标 SNP。然后,我们使用以前的实验室参数开发了 IVIG 耐药性预测模型。然后,我们使用 2019 年 1 月至 12 月期间在另一家中心就诊的 KD 患儿的数据来验证我们的模型。

结果

分析表明,SMAD5 基因中的 rs10056474 GG、rs746994GG、rs76863441GT、rs16944(CT/TT)和 rs1143627(CT/CC)增加了 KD 患者对 IVIG 耐药的风险(比值比,OR>1)。新的预测模型将 SNP 数据与之前从实验室数据得出的模型相结合,显著提高了开发数据集的受试者工作特征曲线下面积(AUC)(0.832,95%置信区间:0.776-0.878 与 0.793,95%CI:0.734-0.844,P<0.05),并在验证数据集(0.820,95%置信区间:0.730-0.889 与 0.749,95%CI:0.652-0.830,P<0.05)中也显著提高。新检测方法在开发数据集的敏感性和特异性分别为 65.33%(95%置信区间:53.5-76.0%)和 86.67%(95%置信区间:80.2-91.7%),在验证数据集的敏感性和特异性分别为 77.14%(95%置信区间:59.9-89.6%)和 86.15%(95%置信区间:75.3-93.5%)。

结论

分析表明,SMAD5 基因中的 rs10056474 和 rs746994、PLA2G7 基因中的 rs76863441 以及白细胞介素(IL)-1B 基因中的 rs16944 或 rs1143627 与中国人群中 IVIG 耐药性 KD 相关。新模型将 SNP 与实验室数据相结合,提高了预测 IVIG 耐药性 KD 的效率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f25/8236184/db4043445766/12969_2021_582_Fig1_HTML.jpg

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