Yonsei Med J.  2018 Jan;59(1):119-127. 10.3349/ymj.2018.59.1.119.

ITPKC and SLC11A1 Gene Polymorphisms and Gene-Gene Interactions in Korean Patients with Kawasaki Disease

• Kim KY
• Bae YS
• Ji W
• Shin D
• Kim HS
• Kim DS

• KMID: 2418858
• DOI: http://doi.org/10.3349/ymj.2018.59.1.119

Abstract

PURPOSE
Kawasaki disease (KD) is an acute systemic vasculitis. Both the etiology of KD and the erythema of Bacille Calmette-Guérin (BCG) injection sites observed in the disease are poorly understood. We investigated the association between KD and single nucleotide polymorphisms (SNPs) in two candidate genes: inositol 1,4,5-triphosphate 3-kinase (ITPKC), a well-studied KD-associated gene, and solute carrier 11a1 (SLC11A1), which is associated with the hypersensitive reaction to the BCG strain in Koreans.
MATERIALS AND METHODS
Associations between KD and SNPs in two genes were evaluated. Potential associations between BCG injection site erythema and SNPs in two genes were also evaluated. Gene-gene interactions between ITPKC and SLC11A1 in KD and BCG injection site erythema were also analyzed.
RESULTS
Three tagging SNPs in ITPKC and five tagging SNPs in SLC11A1 were genotyped in 299 KD patients and 210 control children. SNP rs28493229 in ITPKC was associated with KD and coronary artery complications. SNP rs77624405 in SLC11A1 was associated with KD. Comparisons of KD patients with and without BCG injection site erythema revealed that SNP rs17235409 in SLC11A1 was associated with erythema; no erythema-associated SNPs in ITPKC were identified. Interactions between ITPKC rs28493229_GG and SLC11A1 rs17235409_GA and between ITPKC rs10420685_GG and SLC11A1 rs17235409_AA were strongly associated with BCG injection site erythema.
CONCLUSION
This study identified several important polymorphisms in the ITPKC and SLC11A1 genes in Koreans. The genetic variants identified in this study affected KD and erythema of BCG injection sites independently and through gene-gene interactions. Also, the effects of the polymorphisms were age-dependent.

Keyword

Kawasaki disease; Korean; polymorphism; gene-gene interaction; ITPKC gene; SLC11A1 gene

MeSH Terms

Asian Continental Ancestry Group/*genetics
BCG Vaccine/administration & dosage
Case-Control Studies
Cation Transport Proteins/*genetics
Child
Child, Preschool
*Epistasis, Genetic
Erythema/complications
Female
Genetic Association Studies
*Genetic Predisposition to Disease
Humans
Infant
Male
Mucocutaneous Lymph Node Syndrome/*genetics
Mutation Rate
Phosphotransferases (Alcohol Group Acceptor)/*genetics
Polymorphism, Single Nucleotide/*genetics
Republic of Korea
BCG Vaccine
Cation Transport Proteins
Phosphotransferases (Alcohol Group Acceptor)

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