Single-Nucleotide Polymorphism rs7251246 in ITPKC Is Associated with Susceptibility and Coronary Artery Lesions in Kawasaki Disease

Ho-Chang Kuo,Shu-Chen Chien,Wei-Chiao Chang,Yu-Wen Hsu,Ying-Hsien Huang,Mao-Hung Lo,Carlo Gaetano

doi:10.1371/journal.pone.0091118

Abstract

Kawasaki disease (KD) is a multi-systemic vasculitis that preferentially affects children. A single nucleotide polymorphism (SNP) in inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) has been identified to be an important polymorphism in the risk of KD. This study was conducted to comprehensively investigate the associations between all tagging SNPs of ITPKC in the risk of KD in a Taiwanese population. A total of 950 subjects (381 KD patients and 569 controls) were recruited. Seven tagging SNPs (rs11673492, rs7257602, rs7251246, rs890934, rs10420685, rs2607420, rs2290692) were selected for TaqMan allelic discrimination assay. Clinical data of coronary artery lesions (CAL) and aneurysms were collected for analysis. A significant association was found between rs7251246 in ITPKC and CAL formation. Haplotype analysis for ITPKC polymorphisms also confirmed this association in the patients with CAL and aneurysm formation. This is the first study to identify that SNP rs7251246 in ITPKC is associated with the severity of KD.

Highlights

Kawasaki disease (KD) is a systemic inflammatory vasculitis which was first reported in 1974 [1]
In 2008, Onouchi et al first identified a functional polymorphism of ITPKC that was significantly associated with the susceptibility to KD and coronary artery lesions (CAL) in both Japanese and US children [8]
ITPKC is a negative regulator of T cells, and it may function as a calcium channel modulator that is involved in controlling immune systems

Summary

Introduction

Kawasaki disease (KD) is a systemic inflammatory vasculitis which was first reported in 1974 [1]. It occurs worldwide and mainly affects children less than 5 years of age, and especially in Asian countries. Korea and Taiwan have the highest reported incidence rates of KD worldwide [2,3,4]. The most serious complication of KD is the development of coronary artery lesions (CAL) [6,7]. KD has become the leading cause of acquired heart diseases in children

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