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Association of an IGHV3-66gene variant with Kawasaki disease
- Source :
- Journal of Human Genetics; May 2021, Vol. 66 Issue: 5 p475-489, 15p
- Publication Year :
- 2021
-
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 variablegene (IGHV) cluster in 14q33.32 was identified (rs4774175; OR = 1.20, P= 6.0 × 10−9). Investigation of nonsynonymous SNVs of the IGHVcluster 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 × 10−10in 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 IGHVregion 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.
Details
- Language :
- English
- ISSN :
- 14345161 and 1435232X
- Volume :
- 66
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- Journal of Human Genetics
- Publication Type :
- Periodical
- Accession number :
- ejs54488853
- Full Text :
- https://doi.org/10.1038/s10038-020-00864-z