Kim Kyu Yeun, Bae Yoon Sun, Ji Woohyuk, Shin Dongjik, Kim Ho Seong, Kim Dong Soo
Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Korea.
Medizen Humancare Inc., Seoul, Korea.
Yonsei Med J. 2018 Jan;59(1):119-127. doi: 10.3349/ymj.2018.59.1.119.
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.
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.
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.
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.
川崎病（KD）是一种急性全身性血管炎。KD的病因以及在该疾病中观察到的卡介苗（BCG）注射部位红斑均了解甚少。我们研究了KD与两个候选基因中的单核苷酸多态性（SNP）之间的关联：肌醇1,4,5 - 三磷酸3 - 激酶（ITPKC），一个研究充分的与KD相关的基因，以及溶质载体11a1（SLC11A1），其与韩国人对BCG菌株的超敏反应相关。
评估了KD与两个基因中SNP之间的关联。还评估了BCG注射部位红斑与两个基因中SNP之间的潜在关联。分析了ITPKC和SLC11A1在KD和BCG注射部位红斑中的基因 - 基因相互作用。
对299例KD患者和210例对照儿童进行了ITPKC中的3个标签SNP和SLC11A1中的5个标签SNP的基因分型。ITPKC中的SNP rs28493229与KD及冠状动脉并发症相关。SLC11A1中的SNP rs77624405与KD相关。对有和没有BCG注射部位红斑的KD患者进行比较发现，SLC11A1中的SNP rs17235409与红斑相关；未在ITPKC中鉴定出与红斑相关的SNP。ITPKC rs28493229_GG与SLC11A1 rs17235409_GA之间以及ITPKC rs10420685_GG与SLC11A1 rs17235409_AA之间的相互作用与BCG注射部位红斑密切相关。
本研究在韩国人中鉴定出ITPKC和SLC11A1基因中的几个重要多态性。本研究中鉴定出的基因变异独立地以及通过基因 - 基因相互作用影响KD和BCG注射部位的红斑。此外，多态性的影响具有年龄依赖性。
