1. Identification of SAMD9L as a susceptibility locus for intravenous immunoglobulin resistance in Kawasaki disease by genome-wide association analysis
- Author
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Ryota Ebata, Kee Soo Ha, Yoshihiro Onouchi, Min Seob Song, Kyung-Yil Lee, Jong-Keuk Lee, Young Mi Hong, Sin Weon Yun, Hiromichi Hamada, Gi Young Jang, Myung-Ki Han, Sejung Sohn, Kyung Lim Yoon, Hong Ryang Kil, Jae-Jung Kim, Jeong Jin Yu, Hyoung Doo Lee, Hiroyuki Suzuki, Gi Beom Kim, and Kaoru Ito
- Subjects
0301 basic medicine ,Pharmacology ,biology ,business.industry ,Mucocutaneous zone ,Genome-wide association study ,Locus (genetics) ,Odds ratio ,medicine.disease ,Systemic inflammation ,030226 pharmacology & pharmacy ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,hemic and lymphatic diseases ,Immunology ,Genetics ,medicine ,biology.protein ,Molecular Medicine ,Kawasaki disease ,medicine.symptom ,Antibody ,business ,Systemic vasculitis - Abstract
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 × 10−5). 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 × 10−6). These results provide new insights into the mechanism of IVIG response in KD.
- Published
- 2019
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