polymorphisms are associated with susceptibility to Kawasaki disease but do not predict intravenous immunoglobulin resistance and coronary artery aneurysms.

INTRODUCTION

Kawasaki disease (KD) is a pediatric vasculitis that can result in coronary artery aneurysm (CAA) formation, which is a dangerous complication. Treatment with intravenous immunoglobulin (IVIg) significantly decreases the risk of CAA, possibly through competitive binding to Fc-gamma receptors (FcRs), which reduces the binding of pathological immune complexes. However, ~20% of children have recrudescence of fever and have an increased risk of CAA. Therefore, we aimed to identify genetic markers at the locus associated with susceptibility to KD, IVIg resistance, or CAA.

MATERIALS AND METHODS

We investigated the association of single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs) at the locus with KD susceptibility, IVIg resistance, and CAA risk using a family-based test (KD susceptibility) and case-control analyses (IVIg resistance and CAA risk) in different cohorts, adding up to a total of 1,167 KD cases. We performed a meta-analysis on IVIg resistance and CAA risk including all cohorts supplemented by previous studies identified through a systematic search.

RESULTS

p.166His was confirmed to be strongly associated with KD susceptibility (Z = 3.17, = 0.0015). In case-control analyses, all of the investigated genetic variations at the locus were generally not associated with IVIg resistance or with CAA risk, apart from a possible association in a Polish cohort for the NA2 haplotype (OR = 2.15, 95% CI = 1.15-4.01, = 0.02). Meta-analyses of all available cohorts revealed no significant associations of the locus with IVIg resistance or CAA risk.

DISCUSSION

Currently known genetic variations at the locus are not useful in prediction models for IVIg resistance or CAA risk.