The IL-1B Gene Polymorphisms rs16944 and rs1143627 Contribute to an Increased Risk of Coronary Artery Lesions in Southern Chinese Children with Kawasaki Disease

Abstract

Background. Kawasaki disease (KD) is a systemic form of self-limited vasculitis in children less than five years old, and the main complication is coronary artery injury. However, the etiology of KD remains unclear. The IL-1B polymorphisms rs16944 GG and rs1143627 AA and their diplotype GA/GA have been associated with significantly increased risk of intravenous immunoglobulin (IVIG) resistance in a Taiwanese population, but the relationship between rs16944 A/G and rs1143627 G/A and coronary artery lesions (CALs) in patients with KD has not been investigated. The present study is aimed at investigating whether the rs16944 A/G and rs1143627 G/A polymorphisms in IL-1B were associated with KD susceptibility and CALs in a southern Chinese population. Methods and Results. We recruited 719 patients with KD and 1401 healthy children. Multiplex PCR was used to assess the genotypes of single nucleotide polymorphisms (SNPs), including two SNPs of IL-1B, rs16944 A/G and rs1143627 G/A. According to the results, no significant association was observed between the IL-1B (rs16944 and rs1143627) polymorphisms and KD risk in the patients compared with the healthy controls in our southern Chinese population. However, in further stratified analysis, we found that children younger than 12 months with the rs16944 GG and rs1143627 AA genotypes of IL-1B had a higher risk of CALs than those with the AA/AG genotypes of rs16944 and GG/AG genotypes of rs1143627 (OR=2.28, 95% CI=1.32-3.95, P=0.0032, adjusted OR=2.33, 95% CI=1.34-4.04, P=0.0027). Conclusions. Our results indicated that there was no association between the rs16944 A/G and rs1143627 G/A gene polymorphisms and KD susceptibility. However, the rs16944 GG and rs1143627 AA genotypes of IL-1B may significantly impact the risk of CAL formation in children younger than 12 months, which may contribute to the pathogenesis of KD. These findings need further validation in multicenter studies with larger sample sizes.

Inhibition of IL-6 in the LCWE Mouse Model of Kawasaki Disease Inhibits Acute Phase Reactant Serum Amyloid A but Fails to Attenuate Vasculitis

“…The cytokine profile of the acute phase of the mouse model also bears strong similarity to that of the human disease, with elevations of IL-1b, TNF-a, IL-6, MCP-1, and IL-10 in the serum, as well as clinical symptoms of dysregulated temperature (20,22). Human transcriptome, human genetic data and experimental murine models of KD all support a key role for IL-1b in the pathogenesis of KD, and also show the effectiveness of the LCWE model in terms of translational features to humans, such as histopathologic and even echocardiographic changes (10)(11)(12)(13)(14)(15)(16)(17)(23)(24)(25)(26).. Furthermore, the mouse model reliably predicts treatment efficacy, including of IVIG treatment (22).…”

Lack of Associations BetweenPAI-1andFXIIIPolymorphisms and Arterial Ischemic Stroke in Children: A Systematic Review and Meta-Analysis

“…Previous study based on Chinese children with KD showed the association of 2 genetic polymorphisms rs16944 GG and rs1143627 AA within IL-1B gene with the risk of coronary artery lesions in children younger than 12 months, which may contribute to the pathogenesis of KD. 43 However, we found no papers on CAD and PAI-1 and FXIII polymorphisms in children. In conclusion, the results of conducted systematic review along with meta-analyses based on large group of pediatric patients and controls showed that both PAI-1 and FXIII polymorphisms are not risk factors for AIS in children.…”

Kawasaki syndrome: role of superantigens revisited

“…There are also increased levels of IL-1, TNF-a, and IL-6, and these cytokines correlate with development of coronary artery disease and IVIG nonresponsiveness [15,22,23]. Gene association studies have implicated polymorphisms in IL-1, TNF-a, IL-6, HLA, and Toll-like receptors indicative of immune responses in KS [24][25][26][27][28]. Finally, treatment of patients with IVIG and aspirin reduces the immune activation associated with this syndrome [29,30].…”