Association of an IGHV3-66 gene variant with Kawasaki disease
- 등재 SCIE, SCOPUS
- OA유형 Green Published, Bronze
- 발행기관 Springer Nature
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000182047
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/s10038-020-00864-z
- PubMed https://pubmed.ncbi.nlm.nih.gov/33106546
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
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 × 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 × 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. © 2020, The Author(s), under exclusive licence to The Japan Society of Human Genetics.
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