Association of an IGHV3-66 gene variant with Kawasaki disease
- Authors
- Johnson, Todd A.; Mashimo, Yoichi; Wu, Jer-Yuarn; Yoon, Dankyu; Hata, Akira; Kubo, Michiaki; Takahashi, Atsushi; Tsunoda, Tatsuhiko; Ozaki, Kouichi; Tanaka, Toshihiro; Ito, Kaoru; Suzuki, Hiroyuki; Hamada, Hiromichi; Kobayashi, Tohru; Hara, Toshiro; Chen, Chien-Hsiun; Lee, Yi-Ching; Liu, Yi-Min; Chang, Li-Ching; Chang, Chun-Ping; Hong, Young-Mi; Jang, Gi-Young; Yun, Sin-Weon; Yu, Jeong-Jin; Lee, Kyung-Yil; Kim, Jae-Jung; Park, Taesung; Lee, Jong-Keuk; Chen, Yuan-Tsong; Onouchi, Yoshihiro
- Issue Date
- 2021
- Publisher
- SPRINGERNATURE
- Citation
- JOURNAL OF HUMAN GENETICS, v.66, no.5, pp.475 - 489
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF HUMAN GENETICS
- Volume
- 66
- Number
- 5
- Start Page
- 475
- End Page
- 489
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/138471
- DOI
- 10.1038/s10038-020-00864-z
- ISSN
- 1434-5161
- Abstract
- In a meta-analysis of three GWAS for susceptibility to Kawasaki disease (KD) conducted in Japan, Korea, and Taiwan and follow-up studies with a total of 11,265 subjects (3428 cases and 7837 controls), a significantly associated SNV in the immunoglobulin heavy variable gene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P = 6.0 x 10(-9)). Investigation of nonsynonymous SNVs of the IGHV cluster in 9335 Japanese subjects identified the C allele of rs6423677, located in IGHV3-66, as the most significant reproducible association (OR = 1.25, P = 6.8 x 10(-10) in 3603 cases and 5731 controls). We observed highly skewed allelic usage of IGHV3-66, wherein the rs6423677 A allele was nearly abolished in the transcripts in peripheral blood mononuclear cells of both KD patients and healthy adults. Association of the high-expression allele with KD strongly indicates some active roles of B-cells or endogenous immunoglobulins in the disease pathogenesis. Considering that significant association of SNVs in the IGHV region with disease susceptibility was previously known only for rheumatic heart disease (RHD), a complication of acute rheumatic fever (ARF), these observations suggest that common B-cell related mechanisms may mediate the symptomology of KD and ARF as well as RHD.
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