Homozygous of MRP4 Gene rs1751034 C Allele Is Related to Increased Risk of Intravenous Immunoglobulin Resistance in Kawasaki Disease

Abstract

Background: Kawasaki disease (KD) is a systemic vasculitis in childhood, which mainly causes damage to coronary arteries, and intravenous immunoglobulin (IVIG) is the initial therapy. IVIG resistance increased risk of coronary complication in KD. And genetic background is involved in the occurrence of IVIG resistance. Our previous study indicated the susceptibility of Multi-drug resistance protein 4 (MRP4) SNPs to KD. This study was to clarify the relationship between MRP4 polymorphisms and IVIG resistance.Methods: We genotyped the six polymorphisms of MRP4 gene in 760 cases of KD using Taqman methods.Results: Among the six polymorphisms, only the rs1751034 polymorphism was significantly associated with IVIG resistance in KD [CC vs. TT: adjusted odds ratio (OR) = 2.54, 95% confidence interval (CI) = 1.21–5.34; CC vs. TT/TC: adjusted OR = 2.33, 95% CI = 1.12–4.83, p = 0.023]. Combined analysis of three polymorphisms indicated that patients with 3–6 risk genotypes exhibited significantly elevated risk of IVIG resistance, when compared with those with 0–2 risk genotypes (adjusted OR = 1.52, 95% CI = 1.04–2.22, p = 0.0295). Stratified analysis revealed that in term of age and gender, rs1751034 CC carriers were associated with increased risk of IVIG resistance in those aged ≤ 60 months (adjusted OR = 2.65, 95% CI = 1.23–5.71, p = 0.0133). The presence of three or more risk genotypes was significantly associated with risk of IVIG resistance in children younger than 5 years of age and males.Conclusion: Our results suggest that MRP4 rs1751034 CC is associated with increased risk of IVIG resistance in KD.

The Associated of the Risk of IVIG Resistance in Kawasaki Disease with ZNF112 Gene and ZNF180 Gene in a Southern Chinese Population

“…In the early years, our team has been focused on the progress of KD disease and the therapeutic effect, and achieved some exciting results. We found that single nucleotide polymorphisms (SNPs) of several genes (P2RY12, MRP4 and EIF2AK4 [35][36][37] ) were closely associated with IVIG treatment efficacy in KD; interestingly, these genes played important roles in immune response and cardiovascular-related functions. This study was the first one to focus on the effect of ZNF family (ZNF180 and ZNF112) on IVIG treatment resistance of KD.…”

Risk-prediction models for intravenous immunoglobulin resistance in Kawasaki disease: Risk-of-Bias Assessment using PROBAST

“…Epigenetic inheritance and gene polymorphism may affect the occurrence of IVIG resistance by analyzing the blood samples of children with Kawasaki disease. [58][59][60] Therefore, it is necessary to conduct a multicenter genetic study on a large sample of children with IVIG-resistant Kawasaki disease to explore the predictive role of genetic factors on IVIG resistance. (4) Inflammatory factors are dynamic and vary with the course of the disease, and parameters that predict resistance to IVIG may vary depending on the duration of disease prior to treatment with IVIG.…”

The EIF2AK4/rs4594236 AG/GG Genotype Is a Hazard Factor of Immunoglobulin Therapy Resistance in Southern Chinese Kawasaki Disease Patients

“…Our team has worked on the area of the etiology and therapy effect of KD for many years ( Che et al, 2018 ; Lin et al, 2021 ; Wang et al, 2021 ). We found that the single-nucleotide polymorphism (SNP) of immune and/or cardiovascular-related genes were usually related to IVIG therapy outcome of KD, such as IL-1β ( Fu et al, 2019 ), PLA2G7 ( Gu et al, 2020 ), P2RY12 ( Wang et al, 2020 ), and MRP4 ( Wang et al, 2021 ). However, evidence regarding the polymorphisms of EIF2AK4 and IVIG resistance of KD is very scarce.…”