Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
Department of Pediatrics, Chung-Ang University Hospital, Seoul, Korea.
Pharmacogenomics J. 2020 Feb;20(1):80-86. doi: 10.1038/s41397-019-0085-1. Epub 2019 Apr 11.
Kawasaki disease (KD) is a systemic vasculitis affecting infants and children; it manifests as fever and signs of mucocutaneous inflammation. Intravenous immunoglobulin (IVIG) treatment effectively attenuates the fever and systemic inflammation. However, 10-20% patients are unresponsive to IVIG. To identify genetic variants influencing IVIG non-response in KD, a genome-wide association study (GWAS) and a replication study were performed using a total of 148 IVIG non-responders and 845 IVIG-responders in a Korean population. rs28662 in the sterile alpha motif domain-containing protein 9-like (SAMD9L) locus showed the most significant result in the joint analysis of GWAS and replication samples (odds ratio (OR) = 3.47, P = 1.39 × 10). The same SNP in the SAMD9L locus was tested in the Japanese population, and it revealed a more significant association in a meta-analysis with Japanese data (OR = 4.30, P = 5.30 × 10). These results provide new insights into the mechanism of IVIG response in KD.
川崎病（KD）是一种影响婴儿和儿童的全身性血管炎，表现为发热和黏膜皮肤炎症迹象。静脉注射免疫球蛋白（IVIG）治疗可有效减轻发热和全身炎症。然而，10-20%的患者对 IVIG 无反应。为了确定影响 KD 中 IVIG 无反应的遗传变异，对韩国人群中的 148 名 IVIG 无反应者和 845 名 IVIG 反应者进行了全基因组关联研究（GWAS）和复制研究。在 GWAS 和复制样本的联合分析中，SAMD9L 基因座中的 rs28662 显示出最显著的结果（比值比（OR）=3.47，P=1.39×10）。在日本人群中测试了 SAMD9L 基因座中的相同 SNP，在与日本数据的荟萃分析中显示出更显著的关联（OR=4.30，P=5.30×10）。这些结果为 KD 中 IVIG 反应的机制提供了新的见解。
