Association of the IL16 Asn1147Lys polymorphism with intravenous immunoglobulin resistance in Kawasaki disease
- 주제(기타) Genetics & Heredity
- 설명문(일반) [Kim, Hea-Ji; Kim, Jae-Jung; Lee, Jong-Keuk] Univ Ulsan, Asan Inst Life Sci, Coll Med, Seoul, South Korea; [Yun, Sin Weon] Chung Ang Univ Hosp, Dept Pediat, Seoul, South Korea; [Yu, Jeong Jin; Park, In-Sook; Hong, Soo-Jong; Kim, Kwi-Joo] Univ Ulsan, Dept Pediat, Asan Med Ctr, Coll Med, Seoul, South Korea; [Yoon, Kyung Lim] Kyung Hee Univ Hosp Gangdong, Dept Pediat, Seoul, South Korea; [Lee, Kyung-Yil; Hwang, Ja-Young; Rhim, Jung-Woo] Catholic Univ Korea, Daejeon St Marys Hosp, Dept Pediat, Daejeon, South Korea; [Kil, Hong-Ryang] Chungnam Natl Univ Hosp, Dept Pediat, Daejeon, South Korea; [Kim, Gi Beom] Seoul Natl Univ, Dept Pediat, Childrens Hosp, Seoul, South Korea; [Han, Myung-Ki; Jun, Hyun Ok] Univ Ulsan, Gangneung Asan Hosp, Dept Pediat, Kangnung, South Korea; [Song, Min Seob] Inje Univ, Dept Pediat, Paik Hosp, Busan, South Korea; [Lee, Hyoung Doo] Pusan Natl Univ Hosp, Dept Pediat, Busan, South Korea; [Ha, Kee Soo; Jang, Gi Young; Nam, Hyo-Kyoung; Byeon, Jung-Hye] Univ Korea Hosp, Dept Pediat, Seoul, South Korea; [Hong, Young Mi; Sohn, Sejung] Ewha Womans Univ Hosp, Dept Pediat, Seoul, South Korea; [Kim, Dong Soo] Severance Childrens Hosp, Dept Pediat, Seoul, South Korea; [Lee, Jae-Moo; Kim, Jong-Duk] Seoul Clin Labs, Seoul, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000169141
- 본문언어 영어
- Published As https://dx.doi.org/10.1038/s10038-020-0721-2
- PubMed https://pubmed.ncbi.nlm.nih.gov/31965063
초록/요약
Kawasaki disease (KD) is an acute, self-limited vasculitis, mainly affecting children younger than 5 years old, with accompanying fever and signs of mucocutaneous inflammation. Intravenous immunoglobulin (IVIG) is the standard treatment for KD; however, similar to 15% of patients are resistant to IVIG treatment. To identify protein coding genetic variants influencing IVIG resistance, we re-analyzed our previous genome-wide association study (GWAS) data from 296 patients with KD, including 101 IVIG non-responders and 195 IVIG responders. Five nonsynonymous SNPs (nsSNPs) in five immune-related genes, including a previously reported SAMD9L nsSNP (rs10488532; p.Val266Ile), were associated with IVIG non-response (odds ratio [OR] = 1.89-3.46, P = 0.0109-0.0035). In a replication study of the four newly-identified nsSNPs, only one in the interleukin 16 (IL16) gene (rs11556218, p.Asn1147Lys) showed a trend of association with IVIG non-response (OR = 1.54, P = 0.0078). The same IL16 nsSNP was more significantly associated with IVIG non-response in combined analysis of all data (OR = 1.64, P = 1.25 x 10(-4)). Furthermore, risk allele combination of the IL16 CT and SAMD9L TT nsSNP genotypes exhibited a very strong effect size (OR = 9.19, P = 3.63 x 10(-4)). These results implicate IL16 as involved in the mechanism of IVIG resistance in KD.
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