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Association of an IGHV3-66 gene variant with Kawasaki disease
- Title
- Association of an IGHV3-66 gene variant with Kawasaki disease
- Authors
- Johnson T.A.; Mashimo Y.; Wu J.-Y.; Yoon D.; Hata A.; Kubo M.; Takahashi A.; Tsunoda T.; Ozaki K.; Tanaka T.; Ito K.; Suzuki H.; Hamada H.; Kobayashi T.; Hara T.; Chen C.-H.; Lee Y.-C.; Liu Y.-M.; Chang L.-C.; Chang C.-P.; Hong Y.-M.; Jang G.-Y.; Yun S.-W.; Yu J.-J.; Lee K.-Y.; Kim J.-J.; Park T.; Lee J.-K.; Chen Y.-T.; Onouchi Y.; Korean Kawasaki Disease Genetics Consortium; Taiwan Kawasaki Disease Genetics Consortium; Taiwan Pediatric ID Alliance; Japan Kawasaki Disease Genome Consortium
- Ewha Authors
- 홍영미
- SCOPUS Author ID
- 홍영미
- Issue Date
- 2021
- Journal Title
- Journal of Human Genetics
- ISSN
- 1434-5161
- Citation
- Journal of Human Genetics vol. 66, no. 5, pp. 475 - 489
- Publisher
- Springer Nature
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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 × 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.
- DOI
- 10.1038/s10038-020-00864-z
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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