Abstract
BackgroundHere, 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.MethodsData 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.ResultsAnalysis 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.ConclusionAnalysis 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.
Highlights
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
Target gene selection and genotype detection First, we retrieved literature published before 2015 from the human genome retrieval website provided by the NCBI, and selected 18 Single nucleotide polymorphism (SNP) that may be associated with IVIG resistance in patients with KD [16,17,18,19,20,21,22,23,24]. (Supplementary Table 1) We evaluated the distribution of these SNPs in healthy
This analysis revealed that the rs16944 and rs1143627 loci in the interleukin (IL)-1B gene were in complete Linkage disequilibrium (LD) (D′ = 1.0, r2 = 0.974) and that
Summary
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. Several scoring systems comprising clinical features and laboratory data have been proposed to predict IVIG resistant in KD patients representing various geographic locations and ethnicities with good sensitivity and specificity for the respective source populations [7,8,9,10,11]. These systems are not sufficient for other populations [12], indicating that IVIG resistance might be related to genetic and ethnic factors. The present study was designed to investigate the genes associated with IVIG resistance in a Chinese population and investigate whether combining this genetic information with the existing scoring system could improve the predictive efficacy
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